Human Nutrition and Metabolism
Research Communication
Red Wine Is a Poor Source of
Bioavailable Flavonols in Men1
(Manuscript received 9 August 2000. Initial review completed 13
September 2000. Revision accepted 11 December 2000.)
Jeanne H. M. de Vries,*2 Peter C. H. Hollman,†
Ingrid van Amersfoort,* Margreet R. Olthof* and
Martijn B. Katan*
*Division of Human Nutrition and Epidemiology, Wageningen
University, 6703 HD Wageningen, the Netherlands and †State
Institute for Quality Control of Agricultural Products (RIKILT), 6708
PD Wageningen, the Netherlands
ABSTRACT Red wine is a source of polyphenolic antioxi-
dants, of which flavonols such as quercetin are represen-
tatives. Red wine might therefore prevent LDL oxidation
and atherosclerosis. However, data on the bioavailability of
flavonols from wine are lacking. Therefore, we compared
the bioavailability of flavonols, especially quercetin, from
red wine with that from the major dietary sources, yellow
onions and black tea. Twelve healthy men consumed 750
mL red wine, 50 g fried onions or 375 mL of black tea, each
for 4 d in random order. These supplements provided sim-
ilar amounts of quercetin (14 –16 mg). There was a washout
period of 3 d between each period of supplementation. The
plasma quercetin concentration after the consumption of
wine was lower than that after onions (P < 0.05) and not
different from that after tea. Urinary excretion of quercetin
after wine did not differ from that after onions and was
higher than that after tea (P < 0.05). We conclude that
flavonols from red wine are absorbed. However, because
one glass of red wine provides fewer available flavonols
than one portion of onions or one glass of tea, red wine
appears to be a poorer source of flavonols than these other
two sources. J. Nutr. 131: 745–748, 2001.
● humans ● red wine ● quercetin ● flavonols
KEY WORDS:
● flavonoids
Red wine contains phenolics such as flavonols, catechins,
resveratrol (Constant 1997, Goldberg et al. 1996, Hertog et al.
1993, Kühnau 1976, Siemann and Creasy 1992), anthocyanins
and proanthocyanidins (Mazza 1995). These compounds are
thought to have antioxidative properties that could protect
LDL from oxidation (Abu-Amsha et al. 1996, De Whalley et
1
This work was supported by grants of the Netherlands Heart Foundation
(93.084) and the Foundation for Nutrition and Health Research.
2
To whom correspondence should be addressed at Division of Human Nu-
trition and Epidemiology, Wageningen University, Bomenweg 2, 6703 HD
Wageningen, the Netherlands. E-mail: Jeanne.devries@staff.nutepi.wau.nl
0022-3166/01 $3.00 © 2001 American Society for Nutritional Sciences.
745
al. 1990, Frankel et al. 1993, Kanner et al. 1994, Kinsella et al.
1993, Kondo et al. 1994, Lanningham-Foster et al. 1995,
Rice-Evans et al. 1996). The wine phenolics quercetin, epi-
catechin and resveratrol protected LDL from oxidation in
vitro (Frankel et al. 1993, Kerry and Abbey 1997, Margetts
and Nelson 1991). The strongest effects were seen for querce-
tin and epicatechin. However, data from studies investigating
ex vivo effects on protection of LDL oxidation are contradic-
tory. Some studies (Fuhrman et al. 1995, Nigdikar et al. 1998)
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found that LDL oxidation was inhibited after the drinking of
red wine, whereas others (Caccetta et al. 2000, de Rijke et al.
1996) did not find this effect. Thus, it is still not proved that
phenolics in red wine truly have an effect.
To have any direct effect on LDL oxidation, phenolics have
to be absorbed into the blood. However, data on the absorp-
tion of phenolics from wine, especially flavonols, are sparse,
and it is not yet known to what extent these components are
bioavailable.
Hollman et al. (1996) developed a sensitive and accurate
method to determine flavonols in plasma and urine. Using this
method, we found that quercetin and kaempferol from onions,
apples and tea were absorbed (de Vries et al. 1998, Hollman et
al. 1995), but the extent of absorption differed (Hollman et al.
1997 and 1999). To determine whether the bioavailability of
quercetin from wine is similar to that of other sources in the
diet, we compared quercetin levels in plasma and urine after
the consumption of equal amounts of quercetin from red wine,
tea or onions. In addition, we determined the levels of
kaempferol and isorhamnetin, two other major flavonols.
MATERIALS AND METHODS
Subjects and study design. The Medical Ethics Committee of
the Division of Human Nutrition and Epidemiology approved the
study. We recruited subjects via posters and local newspapers. To
ensure that subjects could tolerate the alcohol in the wine, we only
allowed men with a consumption of at least seven drinks per week to
participate.
The subjects were thoroughly informed about the study, and all
gave their written informed consent. They were medically evaluated
and considered healthy by a physician. The mean ⫾ SD age of the 12
subjects was 24.8 ⫾ 10.4 y, and their body mass index was 22.1 ⫾ 2.1
kg/m2 .
The subjects were randomly assigned to one of three groups. They
followed three treatment periods of 1 wk each. On d 4 –7 of each
treatment period, the subjects consumed red wine, onions or tea. In
this way there was a washout period of 3 d between the periods. Each
of the three groups received the treatments in a different order.
Throughout the study, the subjects consumed a diet low in flavonols.
They were asked not to consume anything from a list with vegetables
and fruits containing ⬎15 mg quercetin/kg, beverages containing ⬎4
mg quercetin/L (Hertog et al. 1992 and 1993) and vegetables con-
taining ⬎5 mg kaempferol/kg.
Supplements. During treatment periods, the subjects consumed
either six 125-mL glasses of red wine, 50 g fried yellow onions or three
125-mL cups of black tea per d. The wine originated from the Médoc
region in France (Chateau Latour St. Bonnet 1993) and was selected
746 DE
for its high content of quercetin. All bottles of wine were taken from
one lot, and the concentration of quercetin was 19 ⫾ 0.3 mg/L (n
⫽ 5). The yellow onions were provided in aluminum trays, and the
black instant tea was made by the subjects from 0.5 g extract/cup.
The daily amount of quercetin provided by the three foods was
almost the same. Thus, the wine provided 14.2 ⫾ 0.3 mg (⫾SD)
quercetin, 1.5 ⫾ 0.1 mg kaempferol, 1.6 ⫾ 0.0 mg isorhamnetin and
6.7 ⫾ 0.1 mg myricetin per d. The fried onions provided 15.9 ⫾ 0.5
mg quercetin, 0.1 ⫾ 0.0 mg kaempferol, 0.6 ⫾ 0.0 mg isorhamnetin
and no detectable amounts of myricetin per d. The tea provided 13.7
⫾ 1.6 mg quercetin, 8.7 ⫾ 1.6 mg kaempferol, no isorhamnetin and
2.7 ⫾ 0.3 mg myricetin per d. We told the subjects to consume one
third of the wine or tea at lunch, one third at dinner and one third
between 2200 and 2400 h; the consumption of onions was divided
between lunch and dinner.
All empty wine bottles, onion trays and tea bags were returned to
the division. We checked dietary compliance by 24-h recalls once a
week. Energy and nutrient intakes were calculated using the Dutch
nutrient database (Stichting Nederlands Voedingsstoffenbestand
1993), and intakes of quercetin and kaempferol were calculated using
our published values for contents in vegetables, fruit and beverages
(Hertog et al. 1992 and 1993). Medications were not allowed except
for contraceptives and acetaminophen (paracetamol). We provided
all subjects with a diary and asked them to record all deviations from
the guidelines.
Blood sampling. Venous blood samples were taken in each
period as previously described (Hollman et al. 1996). All subjects
provided a baseline blood sample on the morning of d 4 of the 2nd
wk, after they had followed the dietary guidelines for 3 d and before
they had started to consume the second series of supplements. On d
7 of each period, the subjects provided two blood samples: one
between 1400 and 1500 h and one between 1700 and 1800 h.
Urine sampling. Five of 12 subjects collected urine for a baseline
value on d 3 of wk 3 after they had consumed the low flavonol diet
for 2 d and before they consumed the third series of supplements. All
12 subjects collected their urine during 24 h on d 7, the last day of
each treatment period.
We provided each subject with ten 500-mL bottles with 2.5 mL
thymol dissolved in isopropanol as a preservative and one 1000-mL
bottle with 5 mL thymol. Subjects collected all urine samples until
the next morning, including the first urine after getting up. The urine
samples were immediately put into polystyrene boxes containing dry
ice. Within 1–5 d, the urine samples were thawed at 40°C. Urine
samples were pooled for each subject per day and stored at ⫺40°C
until analyses.
To check the completeness of urine sampling, we used lithium as
a marker. Each morning for 21 d the subjects consumed 235 ␮mol
lithium (2 mg) as lithium chloride dissolved in 10 mL water as a
marker. The dose is 1% of that used for patients with bipolar disorder
(anonymous 1980). The recovery of orally ingested lithium over a
period of 6 d is ⬃95% (Sanchez-Castillo et al. 1987a and 1987b).
Analytical methods. Quercetin, kaempferol and their conjugates
were simultaneously extracted from plasma or urine and hydrolyzed to
the aglycone with 2 mol HCl/L in aqueous methanol (Hollman et al.
1997) and determined by HPLC with fluorescence detection (Holl-
man et al. 1996). The limit of detection was 0.003 ␮mol/L for
quercetin and 0.002 ␮mol/L for kaempferol and isorhamnetin in
plasma and urine.
A separate undiluted urine sample was acidified and analyzed for
lithium through atomic absorption spectrophotometry (anonymous
1976).
Lithium recovery. Recoveries of lithium in urine were 96 ⫾ 12%
after wine, 100 ⫾ 6% after onions and 98 ⫾ 9% after tea. The
recovery of 12 of the 36 urine samples was ⬍85% or ⬎105%. This
could mean that subjects did not take their lithium or sampled too
much or too little urine, and urinary excretion could be considered
mistakenly too high or too low. However, reanalysis of our data with
correction for lithium recovery did not change the differences we
found among treatments.
The diets. According to diaries, the number of empty packages
and 24-h recalls, the subjects complied well with the dietary guide-
lines. They consumed negligible amounts of flavonol-rich foods dur-
VRIES ET AL.
FIGURE 1 Estimated plasma concentrations of quercetin that will
be reached after the consumption of one portion of wine (100 mL), fried
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yellow onions (15 g) or black tea (125 mL), all with average quercetin
concentration as found in commercially available foods (Hertog et al.
1992 and 1993). The differences in bioavailability among the three
foods are based on plasma concentrations of 12 men who consumed
750 mL red wine, 50 g fried onions or 375 mL strong black tea.
ing the study. The only differences in intake from the diet without
the supplements between the treatments were the intake of energy,
which was lower in the tea period than in the wine period, and the
intake of alcohol, which was significantly higher in the tea period.
Statistical analysis. To analyze the effects of red wine, onions
and tea in plasma, the mean flavonol concentrations of the two
afternoon blood samples were used. To achieve normality, the
amounts of quercetin, kaempferol and isorhamnetin analyzed in
plasma and urine were converted to log10 values. The effects of red
wine, onions and tea were analyzed by using the General Linear
Model procedure (analysis of variance, fixed effect) of the Statistical
Analysis System (SAS Institute 1989) with subject and treatment as
class variables. We found no treatment order effect. The significance
of differences was determined by paired t tests (least significant
difference procedure). A P-value of ⬍0.05 was considered to be
significant.
We used Pearson correlation coefficients to determine the rela-
tionship between plasma concentrations and urinary excretions of
flavonols and that between the first and second times that blood was
sampled, and 95% confidence intervals (CI)3 were calculated using
Fisher’s Z transformation. We calculated within- and between-person
variations for quercetin levels in plasma and urine using the SAS
procedure VARCOMP.
To compare the bioavailability of quercetin from one common
portion of red wine with that of onions and tea (Fig. 1), we first
calculated the relative bioavailability from each food as the rise in
plasma quercetin divided by the amount of quercetin consumed in
this study. We then multiplied this figure by the amount of quercetin
provided by one average portion (Donders-Engelen et al. 1997, Her-
tog et al. 1992 and 1993). Thus, for red wine, one glass contains 100
mL, which provides 0.8 mg (average concentration 8 mg/L). This was
then multiplied by the concentration of 26 nmol/L found in plasma
and divided by the14.2 mg quercetin/d given in this study.
RESULTS
After the three treatments, flavonol concentrations in
plasma were up to five times and excretions in urine were up
to nine times higher than values during baseline (Tables 1 and
2). Plasma concentrations of quercetin and of the sum of the
flavonols quercetin, kaempferol and isorhamnetin were lower
after treatment with wine than after onions (P ⬍ 0.05) and
not different from those after black tea (Table 1).
Urinary excretions suggested that the absorption of quer-
cetin from wine was between absorptions from onions and tea.
The absolute urinary excretion of quercetin after red wine
3
Abbreviation used: CI, confidence interval.
 POOR BIOAVAILABILITY OF FLAVONOLS FROM RED WINE
TABLE 1
Baseline concentrations and effects of daily consumption
of 750 mL red wine (14 mg quercetin), 50 g fried onions
(16 mg quercetin) and 375 mL black tea (14 mg quercetin) on
concentrations of flavonols in plasma of healthy men1
Treatment
Flavonol Baseline Wine Onions Tea
nmol/L
Quercetin* 10 ⫾ 3 26 ⫾ 10a 53 ⫾ 17b 26 ⫾ 13a
Kaempferol* 3⫾3 3 ⫾ 3a 3 ⫾ 0a 14 ⫾ 7b
Isorhamnetin 3⫾3 9 ⫾ 6b 6 ⫾ 3a 3 ⫾ 3a
Sum 16 38 62 43
1 Values are means ⫾ SD, n ⫽ 12; average of two blood samples per
subject. Values in a row with different superscript letters differ signifi-
cantly, P ⬍ 0.05.
tended to be lower than that after onions (P ⫽ 0.09), but it
was significantly higher (P ⬍ 0.05) than that after black tea
(Table 2). The amount of quercetin excreted in urine relative
to intake was on average 0.8% after red wine, 1.0% after
onions and 0.6% after tea. The excretion of the sum of all
determined flavonols, i.e., quercetin plus kaempferol plus
isorhamnetin, was lowest after wine.
Plasma concentrations of flavonols agreed well between the
blood samples taken between 1400 and 1500 h and between
1700 and 1800 h This was shown by high Pearson correlation
coefficients between the quercetin concentrations of flavonols
of all treatment periods (n ⫽ 36): 0.93 (95% CI 0.76 – 0.98)
for quercetin, 0.70 (95% CI 0.48 – 0.84) for kaempferol and
0.85 (95% CI 0.72– 0.92) for isorhamnetin.
The variation in plasma quercetin within persons between
the first and second blood samples on the same day was 9%
after all supplements, and the variation between subjects was
14% after wine, 11% after onions and 20% after tea.
DISCUSSION
We investigated whether the bioavailability of quercetin
from red wine is higher than that from other sources from the
diet. We found that plasma concentrations of quercetin after
the intake of similar amounts of quercetin from red wine were
lower than those after the consumption of onions and not
different from those after the consumption of tea. Urinary
excretions of quercetin were between those of tea and onions.
These results suggest that the bioavailability of quercetin from
red wine is less than that from onions and only slightly better
than that from tea. In addition, the sum of the three flavonols,
quercetin, kaempferol and isorhamnetin, was lowest after red
wine consumption in both plasma and urine.
To increase the precision of the measurements, we selected
wine for its high quercetin concentration and used tea that was
about twice as strong as tea usually consumed in our country
(Hertog et al. 1993). We estimate that the consumption of one
glass (100 mL) of average red wine with a concentration of
quercetin of 8 mg/L (Hertog 1994) would produce plasma
quercetin levels much lower than those after the consumption
of 1 cup (125 mL) of average tea or 1 spoonful (15 g) of fried
onions (Fig. 1).
We did not directly measure the absorption of flavonols but
rather measured it indirectly through an assessment of their
747
concentrations in plasma and urine. It is possible that fla-
vonols from red wine are metabolized differently than those
from onions or tea. For example, the alcohol in the wine could
have influenced the rate of metabolism. However, the urinary
excretion of quercetin after wine and onion consumption was
similar, which argues against such an effect of alcohol. In
addition, the extent to which plasma total (⫹)-catechin,
another polyphenol, increased after the consumption of red
wine was not affected by the coingestion of alcohol (Bell et al.
2000). Plasma quercetin after wine consumption indicates that
the bioavailability of quercetin from red wine is only half of
that from onions. However, urinary excretion suggests that
these differences in bioavailability are smaller. In our previous
studies (de Vries et al. 1998, Hollman et al. 1997), the bio-
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availability of flavonols as determined by the area under the
plasma concentration time curve correlated well with urinary
excretion. The higher plasma concentration of quercetin due
to onion consumption might be caused by the fact that the
daily quercetin intake was provided by only two portions of
onions, whereas it was provided by three portions of wine or
tea. Also, excretions of quercetin relative to intake after the
consumption of onions or tea in this study were similar to
those we found previously (de Vries et al. 1998, Hollman et al.
1995). Thus, urinary excretions appear to be suitable to com-
pare the bioavailability of quercetin in different foods.
The absorption of flavonols from foods depends on the form
in which quercetin is present (Hollman et al. 1997 and 1999).
Quercetin is linked with rutinoside or glucoside. The bioavail-
ability of quercetin from the rutinoside is only 20% of that
from glucoside (Hollman et al. 1999). The two components
are likely absorbed differently; quercetin rutinoside is absorbed
from the colon (Hollman et al. 1999), whereas quercetin
glucoside is actively absorbed from the small intestine (Holl-
man et al. 1999). The rutinosides are major flavonoids in tea
and wine, whereas onions contain only glucosides (Goldberg
et al. 1996). Thus, the results from our study, especially with
tea, are consistent with former findings that quercetin conju-
gated with rutinoside as present in red wine and tea is not as
well absorbed as is quercetin glucoside in onions.
We found variations of plasma quercetin within persons of
10% and between persons of 10 –20%. Variations within per-
sons were rather high, but there was a good agreement be-
tween the quercetin concentrations of the first and second
blood samples. This confirms that quercetin concentrations
TABLE 2
Baseline levels and effects of daily consumption of 750 mL
red wine (14 mg quercetin), 50 g fried onions (16 mg
quercetin) and 375 mL black tea (14 mg quercetin) on
concentrations of flavonols excreted in 24-h urine samples of
healthy men1
Treatment
Flavonol Baseline Wine Onions Tea
nmol/24 h
Quercetin* 53 ⫾ 33 371 ⫾ 109b 507 ⫾ 219b 252 ⫾ 149a
Kaempferol* 80 ⫾ 35 252 ⫾ 87a 332 ⫾ 486a 706 ⫾ 405b
Isorhamnetin* 89 ⫾ 47 335 ⫾ 184b 174 ⫾ 82a 92 ⫾ 85a
Sum 222 958 1013 1050
1 Values are means ⫾ SD, n ⫽ 12; those in a row with different
superscript letters differ, P ⬍ 0.05.
748 DE VRIES ET AL.
stabilize in 4 d, as was shown previously (Hollman et al. 1996).
Variations between persons of quercetin concentrations can be
explained by differences in absorption and metabolism. The
different forms in which quercetin is present in foods might
contribute to the small differences in variance between sub-
jects found for wine, onions and tea.
We conclude that flavonols from red wine are absorbed.
However, the bioavailability of flavonols from red wine is not
better than that from onions or tea. Because one glass (125
mL) of red wine provides lower amounts of available flavonols
than one portion of onions (15 g) or one glass of tea (125 mL),
red wine appears to be a poorer source of flavonols in the diet
than these other two sources.
ACKNOWLEDGMENT
We thank Michel Buijsman for technical assistance.
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