Current Medicinal Chemistry, 2011, 18, 291-300

291

Food Matrix Affecting Anthocyanin Bioavailability: Review

M. Yang1, S.I. Koo1, W.O. Song2 and O.K. Chun*,1
1

Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA
Abstract: Anthocyanins, abundant in deep-colored fruits and vegetables, have received considerable attention due to their
potential health benefits. However, the bioavailability of anthocyanins is relatively low compared to that of other flavonoids. While previous reviews focused on the absorption, metabolism and excretion of anthocyanins, little information is
available on the effects of food matrix on anthocyanin bioavailability, particularly food matrices of the usual diet. The
present review includes the recent studies on interactive effects of anthocyanins and certain food components. Evidence
suggests that the bioavailability of anthocyanins varies markedly depending on food matrices, including other antioxidants
and macronutrients present in foods consumed, which consequently affects the absorption and antioxidant capacity of anthocyanins. Further studies are needed to gain insight into the mechanisms underlying the interactive effects of anthocyanins and food components in their bioavailability and antioxidant capacity of anthocyanins at the physiological level.

Keywords: Anthocyanins, antioxidants interaction, bioavailability, health benefits, food matrix, food synergy.
ANTHOCYANINS: STRUCTURAL PROPERTIES
Anthocyanins belong to a group of flavonoids, a subclass
of polyphenols that contribute to a large proportion of dietary
antioxidant intake [1]. Anthocyanins are water-soluble pigments derived from natural sources, and are responsible for
most of the red, blue, and purple colors of fruits, vegetables,
flowers, and other plant tissues or products [1]. Over 500
different anthocyanins have been isolated from plants. In the
human diet, anthocyanins are widespread in red wine, certain
vegetables (purple cabbages, beans, onions, radishes) and
fruits, particularly, berries. A glass of red wine (3.5 oz) has
20-35 mg anthocyanins, whereas a cup of berries contains
from 15.1 mg in gooseberries to 2,147 mg in chokeberries
[2]. Anthocyanin-rich fruits and vegetables have high antioxidant capacities (ACs) [3-6]. For example, the ACs of
plums and strawberries are higher than those of oranges and
grapefruits rich in flavonols and flavanones [6, 7]. Berries
are ranked high in total antioxidant capacity (TAC) defined
as the cumulative and synergistic potential of various antioxidants present in the biological samples [8, 9]. The consumption of anthocyanins in the United States was overestimated to be 180215 mg/day as reported earlier [10], possibly because the study used inaccurate food intake data [2]. A
recent study, based on the National Health and Nutrition
Examination Survey (NHANES) 2001-2002, showed that the
average intake of anthocyanins in U.S. adults was much
lower and estimated at 12.5 mg/day [2].
Anthocyanins are glycosylated, polyhydroxy or polymethoxy derivatives of 2-phenylbenzopyrylium containing
two benzoyl rings (A and B) separated by a heterocyclic ring
(C) [11]. At different pH, anthocyanins exist in at least four
different structural isoforms, namely, flavylium cations,
hemiketals, quinoid bases, and chalcones [11], and are subgrouped into sugar-free anthocyanidin aglycones and anthocyanin glycosides. In plants, anthocyanins are almost exclusively found in the glycoside forms [12, 13], comprised of a
*Address correspondence to this author at the Department of Nutritional
Sciences, University of Connecticut, 3624 Horsebarn Road Extension Unit
4017, Storrs, Connecticut 06269-4017, USA; Tel: (860) 486-6275; Fax:
(860) 486-3674; E-mail: ock.chun@uconn.edu
0929-8673/11 $58.00+.00

flavylium cation aglycone derivative with the sugar moiety

mainly attached at the 3-position on the C ring or the 5,7position on the A ring [14]. The traditional extraction and
analytical methods for anthocyanins have shown that in
acidic medium, the red flavylium cation is more stable than
other forms [15]. In alkaline medium, most anthocyanins,
except for delphinidin, cyanidin and pelargonidin, degrade to
phenolic aldehyde and respective phenolic acids [12, 16].
Fig. (1) shows the structures of four major isoforms of anthocyanins and several derivatives based on flavylium
cation.
ANTIOXIDANT
PROPERTIES
BENEFITS OF ANTHOCYANINS

AND

HEALTH

Due to their pigmentation and structural characteristics,

anthocyanins have been used as natural colorants in industry.
Anthocyanins possess relatively higher ACs with free radical-scavenging potential than other antioxidants [3-5]. The
antioxidant potential of anthocyanins depends on the chemical structure of the molecule, such as the number of hydroxyl
groups, the catechol moiety in the B ring [17], the oxonium
ion in the C ring [18], the hydroxylation and methylation
pattern [17], and the acylation by phenolic acids [19].
Whether glycosylation of the anthocyanins could modulate
the ACs is controversial as different analytical methods
yielded varied results [20, 21]. The potencies of their antioxidant activities are in the order of delphinidin > petunidin
> malvidin
cyanidin > (+)-catechin > peonidin > pelargonidin [22], as determined by electron spin resonance
(ESR) using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as
the spin trap reagent and a hypoxanthine-xanthine oxidase
(XOD) system as the superoxide radical generator [22].
However, due to the low bioavailability, only a limited
amount of a given anthocyanin reaches the peripheral circulation, despite their high antioxidant potential for health
benefits [23]. Anthocyanins have been found to reduce risks
for chronic diseases through enhancing antioxidant defense
and modulating antioxidant and inflammatory signaling
pathways. They have been shown to restore or elevate the
activities of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) [24, 25],
and increase glutathione contents [26] by activating the anti 2011 Bentham Science Publishers Ltd.

292 Current Medicinal Chemistry, 2011 Vol. 18, No. 2

Yang et al.

Fig. (1). (A) The structures of four major isoforms of anthocyanins under different pH conditions and their corresponding colors of the solution; (B) Selected anthocyanins based on flavylium cation and some derivatives.

oxidant response element upstream of genes that are involved in antioxidation and detoxification [27], or phosphorylating Nuclear factor erythroid 2 (NF-E2)-related factor
2 (Nrf2) [28]. Bei et al. [29] recently reviewed the multiple
anticancer effects of anthocyanins including inhibitions of
the transcription activity of NF-
B and tyrosine receptor
kinase phosphorylation [29-31]. Anthocyanins are also implicated in rescuing the high fat induced transcriptional reprogramming [32], and extending the shortened life span
caused by tumor suppressing gene p53 mutation [33]. In addition, protocatechuic acid, the newly identified anthocyanin
metabolite with a high bioaccessbility and a marked antioxidant activity [29, 34, 35], may contribute to the observed
benefits derived from anthocyanins.
Anthocyanins, as shown by cell and animal studies, attenuate oxidative damage and inflammation [29, 36], repair
DNA damage [37, 38], trigger apoptosis in cancer cells [3941], reduce lipoprotein oxidation [24, 30], normalize lipoprofiles [42], improve vascular endothelial function [43, 44],
decrease platelet reactivity [31], and ameliorate neurotoxicity
[45]. Taken together, anthocyanins are considered antiinflammatory, anti-cancer [29], anti-hemostatic and antiobesity agents [32, 46, 47], which could reduce the risks of
cancer [48, 49], cardiovascular diseases [50, 51], and neurological disorders including Alzheimers disease [52, 53].
Whether anthocyanins have cytotoxicity depends on specific
anthocyanin forms and cell types [54-57]. A recent study
showed that cyanidin and delphinidin preferentially kill cancer cells with high malignant characteristics and resistant to
conventional treatment regimens [54]. Although further
clinical trials are needed to validate the beneficial effects of
anthocyanins in humans, the cited findings above suggest
that anthocyanin-rich foods could make a substantial impact
on human health, especially for those people who frequently

consume berries and other pigmented fruits and vegetables

as a part of their habitual diet.
ABSORPTION AND TRANSPORT OF ANTHOCYANINS DETERMINE THEIR BIOAVAILABILITY
Anthocyanin can be structurally modified during food
processing and storage, and also in vivo environments following ingestion. Several studies used in vitro digestive systems to mimic the upper gastrointestinal (GI) tract and determined the potential bioactivity or metabolism of anthocyanins [58, 59]. Anthocyanins can exist in different forms
in the stomach and intestine, which are the absorption sites
of anthocyanins [13]. In the acidic gastric environment, the
red flavylium cation is the most stable major form. However,
upon entering the basic environment of the upper small intestine, flavylium cation is most likely changed to carbinol
pseudobase which has a limited absorption rate [15]. Glycosidic linkages of anthocyanins are hydrolyzed by microflora
in colon and aglycones are metabolized to form phenolic
acids and/or other unidentified metabolites [16, 60].
During and after absorption, anthocyanins may undergo
glucuronidation and methylation [61, 62]. Several studies in
rats and humans showed that anthocyanins are absorbed and
excreted as intact glycosides without modification [48, 63]
and that nonacylated anthocyanins are more bioavailable
than acylated ones [64]. Anthocyanins may be absorbed into
the intestinal epithelial cells through the glucose transporters
such as glucose transporter 2 (GLUT2) [65] and possibly
Na+/glucose cotransporter 1 (SGLT1) [66]. One recent study
indicated that several anthocyanins may be actively transported out of the intestine and endothelia, limiting their
bioavailability to the circulation [67]. As many of these studies were conducted in animals and cell cultures, further stud-

Food Matrix Affecting Anthocyanin Bioavailability

ies are needed to define factors affecting the absorption, metabolism, and excretion of anthocyanins.
FOOD MATRICES AND ANTHOCYANIN BIOAVAILABILITY
Singly Administered Anthocyanin-Rich Food and Anthocyanin Bioavailability
In numerous animal and human studies using anthocyanin-rich foods, the bioavailability of anthocyanins were
assessed by their plasma concentrations and urinary excretion. In general, the bioavailability of anthocyanins was
lower than that of other flavonoids [13, 67, 68]. The
bioavailability of anthocyanins, as reported in human studies,
is summarized in Table 1. Blueberries, elderberries, blackcurrants, strawberries, red wines and red grapes are common
food samples used. In most of the studies with blueberries,
elderberries and blackcurrants, the percentage of total urinary excretion of anthocyanins, an estimate of apparent absorption, was consistently less than 1% and the maximum
plasma concentrations were calculated at nanomole or
nanogram levels [34, 48, 61, 69-82]. The reported low
bioavailability of anthocyanins may be attributable to multiple factors, as summarized below: a) anthocyanins have poor
stability. Only the four major isoforms, i.e., flavylium
cations, hemiketals, quinoid bases, and chalcones, are well
absorbed and rearranged due to different pH and temperature
in the GI tract [83]; b) anthocyanins undergo biotransformation including glucuronidation and/or sulfation following
ingestion [83], thereby decreasing their structural stability
[68]. Additionally, the metabolites produced by the intestinal
microflora might contribute to the bioavailability of anthocyanins and need to be determined [15, 34, 60, 68, 84]. Some
anthocyanins in the blood stream are readily converted to
protocatechuic acid and other hydroxybenzoic acids which
may not be identified as anthocyanins derivatives [13]; c) a
significant proportion of intestinal degraded products of anthocyanins is likely to interact with their metabolites [96],
which may interfere with the absorption of anthocyanins;d)
anthocyanins can form insoluble complexes with particulates
and bound to bile salts [97]; e) besides the structural properties of anthocyanins, the analytical methods or experimental
procedures used may attribute to the underestimation of the
plasma or urinary levels of anthocyanins. High performance
liquid chromatography (HPLC) has been used as the principal detection method to indirectly measure anthocyanin concentration as red flavylium cations at 530 nm. However, this
structure is not likely to exist in the more alkaline physiological environments. Other anthocyanins, which are probably not able to regenerate flavylium cations in sample preparation steps, may not be detected by HPLC alone [13]. The
isotope labeling of anthocyanins has been strongly recommended to better assess their absorption and metabolism [13,
68]; and f) more importantly, food matrices, including micronutrients and macronutrients, in the anthocyanin-rich
foods or from other food components consumed with anthocyanins, synergistically or antagonistically, may also affect
their bioavailability.
Various types of food samples (Table 1) were used to determine the effects of food matrix on anthocyanin bioavail-

Current Medicinal Chemistry, 2011 Vol. 18, No. 2

293

ability. Anthocyanins in strawberries have been reported

highly bioavailable with their urinary levels reaching more
than 1% [77, 85-87]. Blood oranges have also been suggested as a significant contributor, although limited data are
available [34, 82]. Anthocyanins in red wine is highly
bioavailable up to 5.1% of ingested dose [88], though inconsistent among several reports yielding as low as 0.3% [8992]. The discrepancy in anthocyanin bioavailability from
different food sources, to a large extent, is due to the presence of several structurally diverse anthocyanins in these
foods, and the interactions between food matrix and these
specific anthocyanins. Any one type of fruit which has a very
complex array of anthocyanins may make a bioavailability
study exceedingly difficult. For example, blackcurrants have
four major anthocyanins delphinidin-3-O-glucose, cyanidin-3-O-glucose, delphinidin-3-O-rutinose, and cyanidin3-O-rutinose, while blueberries have more than twenty five
forms of anthocyanins. Compared to other fruits, strawberries, blackberries and blood oranges have relatively simpler
anthocyanin profiles. Strawberries contain one major anthocyanin, pelargonidin-3-O-glucoside and blackberries have
cynidin-3-O-glucoside as the predominant form, whereas
blood oranges contain cynidin-3-O-glucoside and cynidin-3(6-malonyl)-glucoside which comprise over 82% of their
total anthocyanins [15, 87, 98].
In pigs, the total urinary recovery of pelargonidin-3-Oglucoside plus its related metabolites was eight fold higher
than that of cyanidin-3-O-glucoside [99], which may partly
explain the greater bioavailability of anthocyanins from
strawberries than blackberries [100]. In humans, pelargonidin-3-O-glucoside from strawberries was more readily
absorbed compared to other anthocyanin forms, as evidenced
by predominately higher concentrations of its corresponding
metabolite pelargonidin-3-O-glucuronide in urine along
with smaller quantities of other metabolites [77, 85]. Furthermore, feeding studies showed that pelargonidin-3-Oglucuronide, the main metabolite of pelargonidin-3-Oglucoside, had greater bioaccessibility to the blood stream
[15, 77, 94]. Therefore, a lower concentration of pelargonidin-3-O-glucoside in blackberries, when compared to
strawberries, contributed to a lower overall bioavailability.
Although blackberries and blood oranges both have high
proportions of cynidin-3-O-glucoside, the urinary recoveries
in human were very different (0.16% vs 1.2%) [82, 96].
However, a study using blood orange juice with rats showed
that the urinary recovery was markedly low (0.082%) [101].
More studies on anthocyanin bioavailability from blood oranges and blackberries are needed to determine which components in these two fruits differentially affect their bioavailability despite their similar anthocyanin profiles. Besides,
when compared to elderberries, urinary excretions of anthocyanins in blueberries were much lower [61]. The reason for
this may be that individual anthocyanins were present in
smaller amounts in blueberries than in elderberries [61].
Similarly, a study using red wine or red grape juice reported that anthocyanins from red grape juice were more
readily absorbed than that from red wine (urinary excretion
0.23% vs. 0.18%) [89, 90]. The presence of alcohol in red
wine may possibly attribute to the decrease in anthocyanin
absorption [89]. Bub et al. [91] reported that once consumed,
alcohol from red wine may slightly modify the time course

294 Current Medicinal Chemistry, 2011 Vol. 18, No. 2

Table 1.

Yang et al.

Human Studies of Anthocyanins Bioavailability Classified by Common Anthocyanin-Rich Food Matrices

Classification

Specific Source

Total anthocyaninsa

Cmax b

tmax c

Urinary

Ref

excretiond
(% of intake)
Blueberry

Elderberry

Blackcurrant

Strawberry

Red wine

Red Grape

Blood orange
Others

Blueberry (189 g)

690 mg

Blueberry powder (100 g)

1200 mg

Blueberry extract (300 mL)

439 mg

0.004 (6 h)
29 nmol/L

4h
0.02 (7 h)

Elderberry extract (12 g)

720 mg

Elderberry extract (12 g)

720 mg

97 nmol/L

1.2 h

Elderberry extract (12 g)

720 mg

97 nmol/L

1.2 h

Elderberry extract (25 g)

1500 mg

100 ng/mL

0.5 h

Elderberry extract (30 mL)

278 mg

Elderberry extract (30 mL)

147.3 mg

0.077(4 h)

1.74 h

[48]
[61]
[69]

0.06 (24 h)

[78]
[74]

0.39 (< 7 h)

[71]

0.37 (< 7 h)

[76]

Elderberry extract (200 mL)

1852 mg

0.27 (< 7 h)

[71]

Elderberry (11 g)

1900 mg

0.012 (6 h)

[81]

Blackcurrant concentrate (300 mL)

189 mg

0.06 (7 h)

[48]

Blackcurrant concentrate (150 mL)

33.0 mg/kg bwe

5.0-73.4 nmol/L

1.25-1.75
h

0.11 (8 h)

[79]

Blackcurrant juice

2700-4400 mg/kg bwe

16-53 ng/mL

0.75 h

0.07 (4 h)

[70]

Blackcurrant juice (200 mL)

153 mg

0.05 (5 h)

[75]

Blackcurrant juice (137 mL)

144.8 mg

0.04 (7 h)

[76]

Blackcurrant juice (300 g)

33.6 mg

0.079 (48 h)

[80]

Blackcurrant, frozen (100 g)

642 mg

0.075 (48 h)

[80]

1.73 h

Strawberries (200 g)

77.3 mg

1.0 (24 h)

[77]

Strawberries (200 g)

62.3 mg

1.8 (24 h)

[85]

Strawberries
(100 g, 200 g, 400 g)

6.7 mg/100 g

2.0 (24 h)

[86]

Strawberries (100-400 g)

57.1 mol/ 100g

2.35 (24 h)

[87]

Red wine (300 mL)

218 mg

Red wine (400 mL)

279.6 mg

Red wine (400 mL)

180 mg

274 nmol/L

1.1 h

5.1 (12 h)

[88]

42.9 ng/mL

1.5 h

0.18 (7 h)

[89]

43 ng/mL

1.5 h

0.23 (7 h)

[90]

Red wine (500 mL)

68 mg mal-3-glc

1.4 nmol/L

0.8 h

0.02 (6 h)

[91]

Red grape juice (400 mL)

283.5 mg

0.1001 ng/L

0.5 h

0.23 (7 h)

[89]

Red grape juice (400 mL)

284 mg

100 ng/mL

0.5 h

0.18 (7 h)

[90]
[91]

Red grape juice (500 mL)

117 mg mal-3-glc

2.8 nmol/L

2.0 h

0.02 (6 h)

Red grape extract (12 g)

183.8 mg

4.2 nmol/L

2.3 h

0.07 (24 h)

[92]

Blood orange juice (1000 mL)

71mg CyGg

1.9 nmol/L

2h

1.2 (24 h)

[82]

Blood orange juice (600 mg)

21 mg cy-3-glch

8.3 nmol/L
96 nmol/L

[34]

Chokeberry extract (7.1 g)

721 mg

0.15 (24 h)

[93]

Blackberries (200 g)

431 mg

0.16 (24 h)

[94]

Steamed Red Cabbage

(100 g, 200 g, 300 g)

1.38 mol/g

0.083 (24 h)

[95]

Purple carrot juice

(50 ml, 150 ml, 250 ml)

65, 194, 323 mg

2.5-9.6 nmol/L

2.8 h

1-2 h

Total anthocyanins dose in specific food source if not stated otherwise.

Maximal plasma concentration.
Time to reach Cmax .
d
Total urinary excretion (original anthocyanins plus metabolites) as an estimate of apparent absorption, expressed as % of total intake of anthocyanins.
e
bw: body weight.
f
Mal-3-glc = malvidin-3-O-glucoside.
g
CyG includes cyanidin-3-O-glucoside and cyanidin-O-(6-malonyl) glucoside.
h
Cy-3-glc= cyanidin-3-O-glucoside.
b

[61]
[72]

[64]

Food Matrix Affecting Anthocyanin Bioavailability

Current Medicinal Chemistry, 2011 Vol. 18, No. 2

of the increase in the plasma anthocyanin concentration but

did not affect its bioavailability in men. It is possible that
alcohol may have no effect on anthocyanin bioavailability
but slow the rate of absorption [100]. To date, few studies
have compared the effects of different food sources on anthocyanin bioavailability.
Interactions Between Anthocyanins and Food Components
Several studies have combined anthocyanin-rich fruits
with other food components to mimic physiological processes and to examine the influence of meal components on
anthocyanins bioavailability (Table 2). The in vitro and in
vivo studies are insufficient and controversial. Most cell culture and animal studies have reported both positive and negative effect of other foods on anthocyanins. A study, using an
in vitro digestive system to assess the potential bioavailability of anthocyanins, showed that regular foods such as bread
Table 2.

and cooked minced beef could help protect anthocyanins

from raspberry extract in the GI tract [58]. Similarly, ethanol
may enhance the cellular absorption of polyphenols [102]
and the transport of anthocyanins involving GLUT2 through
intestinal epithelial cells [65]. A study with rabbits reported a
higher anthocyanin absorption rate from blackcurrant juice
than from an aqueous citric acid solution of purified anthocyanins [70]. However, when given in citric acid water, an
oral administration of oatmeal to rats slowed the absorption
of anthocyanins from blackcurrant, probably due to reduced
total absorption of anthocyanins from the gut [49]. The two
studies suggest that citric acid or some components in oatmeal such as fibers may interfere with the intestinal absorption of blackcurrant anthocyanins.
Conversely, a number of other studies have shown no
such effect of food matrix. In a study with strawberries with
or without cream in healthy humans, no significant difference was noted in plasma Cmax and urinary excretion between groups, although a delayed tmax was observed in sub-

Selected Studies Related to Food Matrix or Processing Effects on Anthocyanin Bioavailability

Food item

Strawberries

Anthocyanin
source and/or other
food useda

Experiment b

Strawberries (200 g)

Human
studies

Cmax d

Total
anthocyanins

Red wine

Red wine (500 ml)

Blackcurrant + citric
acid water

Human
studies

Rat studies

Blackcurrant + Oatmeal +citric acid

water
Blackcurrant

Blackcurrant juice (6
ml)

Rabbit studies

Blackcurrant concentrate + aqueous

citric acid (6 ml)
Blackcurrant juice
(2.7 g)

Human
studies

Blackcurrant juice
(2.7 g) + a rice cake
Blackcurrant

Fresh blackcurrant
(100 g)

Urinary
excretionf

Major findings

Ref

Cream delayed tmax. Overall bioavailabilities of

anthocyanins were not
different.

[77]

Alcohol did not affect mal3-glc absorption.

[91]

Addition of oatmeal
slowed anthocyanin absorption and excretion but
did not affect metabolism.
There is no change in
bioavailability.

[63]

In rabbits, anthocyanins
from blackcurrant juice
was greater absorbed than
that from an aqueous citric
acid matrix;
In human, the bioavailability was not influenced by
the ingestion of a rice
cake; The rice cake delayed tmax.

[70]

Processed products of
blackcurrants have much
less anthocyanins than
fresh and frozen ones.
Bioavailability is very
poor in any food source.

[80]

(% of intake)

Dealcoholized red
wine (500 ml)
Blackcurrant

tmax e

227
nmol/L

1.1 h

1.0 (24 h)

274
nmol/L

2.4 h

1.33 (24 h)

68 mg mal-3glch

1.4
nmol/L

0.8 h

0.024 (6 h)

58 mg mal-3glch

1.5
nmol/L

1.5 h

0.0224 (6 h)

250 mg

0.37
mol/L

0.25 h

0.03 (7 h)

250 mg

0.20
mol/L

1.0 h

0.02 (7 h)

117 mg/kg

0.5 h

0.035 (4 h)

164 mg/kg bwi

0.5 h

0.0095 (4 h)

222 mol
pel-3-glcg

Strawberries (200g)
+ cream(100ml)

Human
studies

11.6 mg/kg bwi

16 ng/mL

0.75 h

0.048 (4 h)

11.6 mg/kg bwi

32 ng/mL

1.5 h

0.045 (4 h)

897 mg

Frozen blackcurrant
(100 g)

642 mg

0.053 (48 h)

Blackcurrant drink
(300 g)

33.6 mg

0.036 (48 h)

Compare anthocyanins alone with anthocyanins plus other food components.

Human or animal studies.
c
Total anthocyanins dose in specific food source if not stated otherwise.
d
Maximal plasma concentration.
e
Time to reach Cmax.
f
Total urinary excretion (original anthocyanins plus metabolites) as an estimate of apparent absorption, expressed as % of total intake of anthocyanins.
g
Pel-3-glc = pelargonidin-3-O-glucoside.
h
Mal-3-glc = malvidin-3-O-glucoside.
i
bw = body weight.
b

295

296 Current Medicinal Chemistry, 2011 Vol. 18, No. 2

jects consuming strawberries with cream (1.1 0.4 h vs. 2.4

0.5 h, p < 0.001) [77]. These observations are consistent
with an earlier study that the time needed to reach the maximum serum level was significantly delayed when anthocyanins were consumed together with a high fat meal [73]. It was
suggested that the fat present in the cream slowed the transit
of anthocyanins, caused by duodenal and ileal brakes activated by fat [77, 103]. The prolonged gastric emptying
would also slow the appearance of anthocyanins in the small
intestine and hence into the blood, resulting in a slower, but
ultimately equal absorption of anthocyanins [70, 77].
Studies on the effects of sugar on the bioavailability of
anthocyanins have also yielded inconsistent results. Glucose
transporters, SGLT1 and GLUT2, have been reported to
transport cyanidin-3-O-glucoside [65, 66] and malvidin-3-Oglucoside [65]. Sugar moieties within the anthocyanin structures may help pull the compound to cross the intestinal
brush border [81]. In human clinical trials, a decrease in the
urinary excretion of cyanidin-3-O-glucoside has been reported with added sugar, while that of cyanidin-3-Osambubioside was not affected [81]. With sucrose ingestion,
total urinary yield of the ingested dose of anthocyanins from
elderberry juice was lower than that without sucrose (0.028
% vs 0.035 %) [104]. While another study using blackcurrants with or without rice cakes showed that the consumption
of blackcurrant juice with a rice cake delayed the peak
plasma concentration of anthocyanin in healthy women but
had no effect on bioavailability [70]. Carbohydrates accounted for 79% of the rice cake used in this study and yet
had no effect on anthocyanin absorption [70]. Such a difference might probably be explained by the time difference for
carbohydrate digestion and anthocyanin absorption, as tmax
for anthocyanins is usually less than 1 hour. However, the
sugar content of red grape juice may elevate anthocyanin
uptake through the cotransporter, SGLT-1, compared to red
wine, as reported in a crossover study [89]. This discrepancy
may be due to the stronger inhibitory effect of alcohol present in red wine than that of sugar in red grape juice. These
inconsistent findings may be related to the variations in anthocyanin forms in the different food items used. The effect
of sugar on anthocyanin absorption may probably be specific
to different anthocyanins. For example, cyanidin-3-Oglucoside might be inhibited by sugar while others such as
pelargonidin-3-O-glucoside are not. Because there are many
different forms of anthocyanins in any given food item, the
sugar effect on a certain form warrants further exploration.
Besides the combination of anthocyanins with other
foods, the degree and type of food processing have been
shown to affect anthocyanin contents in food without affecting their bioavailability. Processed blackcurrant products,
including fresh fruit juices and smoothies, had a substantially
lower amount of anthocyanins than fresh or frozen blackcurrants [80], which may be attributable to the anthocyanin instability due to exposure to different pH, temperature, light
conditions, and the presence of metal ions or oxygen [11,80].
The low absorption from a processed blackcurrant syrup was
found similar to that from the whole fruit in a randomized
two-phase crossover human trials [80]. In addition, thermal
treatments with the exception of microwave heating, drastically reduced total violet cauliflower anthocyanin content
[105].

Yang et al.

The effect of food components on anthocyanins antioxidant capacity has been also investigated. A crossover human
study demonstrated that ingestion of blueberries resulted in a
greater reducing and chain breaking potential in plasma, but
the consumption of blueberries along with milk had no effect
on the antioxidant-mediated radical scavenging level [106].
Another study showed that blackcurrant juices with water,
but not with defatted milk, could increase the antioxidant
capacity in plasma and urine [107]. The results of these food
combination studies are in agreement with those using other
polyphenols with milk [108, 109]. The findings suggest that
the proteins in milk may chelate the polyphenols and prevent
their absorption via the intestinal cells [110]. Lipids were
also found to interact with milk proteins and antioxidants
[111].
Interactions Between Diverse Antioxidants and Anthocyanins
High consumption of fruits and vegetables has been associated with reduced risks of chronic diseases. However,
singly administered antioxidants in clinical trials do not necessarily have favorable health effects [23, 112]. The synergism among antioxidants such as in vitamin C, vitamin E
and
-carotene [113], vitamin E and ascorbic acid or flavonoids [114], and different polyphenols [115] have been reported. Similarly, anthocyanins and other phytochemicals or
vitamins abundant in fruits may interact with each other synergistically or antagonistically. Anthocyanins and several
phenolics in the blueberry extract may cooperatively regenerate oxidized lipid-soluble antioxidants in the plasma [116].
Malvidin-3-O-glucoside with high antioxidant potential can
be regenerated by catechin, which was relatively ineffective
in inhibiting linoleic acid oxidation in micelles [117]. Catechin can also contribute to the recycling of peonidin-3-Oglucoside to a lower extent [117]. This may be attributed to
the higher spin densities of malvidin-3-O-glucoside and
peonidin-3-O-glucoside on phenolic O atoms, and the destroyed aromaticity in these two anthocyanins, which makes
these products partially saturated and unable to continue to
cycle with catechin [117]. Similar results have also been
observed when catechin was replaced with epicatechin,
which indicated that most common dietary flavonols underwent a synergistic antioxidant effect with common anthocyanins [117]. Additionally, flavonols, in acylated forms,
able to generate corresponding anthocyanins [118], can protect ascorbic acid and anthocyanins from oxidation [119,
120]. This type of interactive effect may be explained by
flavonols interference in the complex formation between
ascorbic acid degradation products and anthocyanins [119],
and their copigment properties [121, 122]. Some flavonoids
(hesperidin, narirutin, naringin and neohesperidin) in blood
orange juice possibly reduce the influence of temperature on
degradation of anthocyanins [123]. Different from the positive effects of many other flavonoids, quercetin-3-Oglucoside inhibited cyanidin-3-O-glucoside absorption in the
mouse intestine [66]. The interaction between ascorbic acid
and anthocyanins, which has attracted much attention, remains controversial as it varies in different fruits. The protective function of ascorbic acid on anthocyanins was shown
in elderberries [123]. Added ascorbic acid was found to protect the anthocyanins in the pomegranate juice from degrada-

Food Matrix Affecting Anthocyanin Bioavailability

tion by hydrogen peroxide treatment [122]. In contrast,

ascorbic acid at a higher concentration (80 mg/L) accelerated
anthocyanins degradation in cherry juice [122] and in blood
orange juice [124]. These differences may be due to the accumulation of degradation products of ascorbic acid reaching
a critical level, which degraded anthocyanins at a rapid rate;
and to the degradation of flavonols which otherwise protect
anthocyanins [122]. Furthermore, the combination of different fruits including orange, apple, grape, and blueberry
showed a synergistic effect in antioxidant activity [23].
Findings from animal studies on anthocyanin interactions
are controversial. Titta et al. [32] found only the blood orange juice, but not purified cyanidin-3-O-glucoside, could
entirely rescue the high fat-induced transcriptional reprogramming and inhibit fat accumulation in mice. However,
supplementation with whole blueberries or strawberries in
mice did not prevent obesity, whereas feeding purified blueberry or strawberry anthocyanins reduced obesity [125]. The
discrepancy may stem from the difference in food matrix and
its influences on anthocyanin bioavailability or various interactions between other nutrients and different forms of anthocyanins. A few human studies have shown that consumption
of blackberry juice caused a significant increase in ascorbic
acid levels and catalase activity in plasma, with no changes
in plasma urate and
-tocopherol levels [107], whereas supplementation with an anthocyanin-rich blueberry beverage
did not significantly affect plasma vitamin C or vitamin E in
young athletes [126].

Current Medicinal Chemistry, 2011 Vol. 18, No. 2

SGLT1

= Na+/glucose cotransporter 1

SDO

= superoxide dismutase

TAC

= total antioxidant capacity

XOD

= xanthine oxidase

297

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As evidence for the health promoting effects of anthocyanins continues to accumulate, considerable attention has
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bioavailability varies depending on their food sources,
chemical forms, food matrices, food processing conditions,
and various physiological factors. Further studies are needed
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bioavailability in relation to health benefits and chronic disease prevention.

[9]

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AC

= antioxidant capacity

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BW

= body weight

DMPO

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ESR

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GI tract

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GLUT2

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GSH-Px = glutathione peroxidase

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HPLC

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NF-
B

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activated B cells

Nrf2

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Received: September 18, 2010

Revised: November 17, 2010

Accepted: November 19, 2010

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