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American Journal of Clinical Nutrition, Vol. 81, No. 1, 230S-242S, January 2005
© 2005 American Society for Clinical Nutrition

DIETARY POLYPHENOLS AND HEALTH: PROCEEDINGS OF THE 1ST INTERNATIONAL CONFERENCE ON POLYPHENOLS AND HEALTH

Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies1,2,3

Claudine Manach, Gary Williamson, Christine Morand, Augustin Scalbert and Christian Rémésy

1 From the Unité des Maladies Métaboliques et Micronutriments, INRA, Saint-Genès Champanelle, France (CMa, CMo, AS, CR), and the Nutrient Bioavailability Group, Nestlé Research Center, Lausanne, Switzerland (GW)

2 Presented at the 1st International Conference on Polyphenols and Health, held in Vichy, France, November 18–21, 2004.

3 Address reprint requests and correspondence to C Manach, Unité des Maladies Métaboliques et Micronutriments, INRA, 63122 Saint-Genès Champanelle, France. E-mail: manach{at}clermont.inra.fr.

ABSTRACT

Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging. Bioavailability differs greatly from one polyphenol to another, so that the most abundant polyphenols in our diet are not necessarily those leading to the highest concentrations of active metabolites in target tissues. Mean values for the maximal plasma concentration, the time to reach the maximal plasma concentration, the area under the plasma concentration-time curve, the elimination half-life, and the relative urinary excretion were calculated for 18 major polyphenols. We used data from 97 studies that investigated the kinetics and extent of polyphenol absorption among adults, after ingestion of a single dose of polyphenol provided as pure compound, plant extract, or whole food/beverage. The metabolites present in blood, resulting from digestive and hepatic activity, usually differ from the native compounds. The nature of the known metabolites is described when data are available. The plasma concentrations of total metabolites ranged from 0 to 4 µmol/L with an intake of 50 mg aglycone equivalents, and the relative urinary excretion ranged from 0.3% to 43% of the ingested dose, depending on the polyphenol. Gallic acid and isoflavones are the most well-absorbed polyphenols, followed by catechins, flavanones, and quercetin glucosides, but with different kinetics. The least well-absorbed polyphenols are the proanthocyanidins, the galloylated tea catechins, and the anthocyanins. Data are still too limited for assessment of hydroxycinnamic acids and other polyphenols. These data may be useful for the design and interpretation of intervention studies investigating the health effects of polyphenols.

Key Words: Polyphenols • flavonoids • isoflavones • flavonols • flavanones • hydroxycinnamic acids • hydroxybenzoic acids • anthocyanins • proanthocyanidins • catechins • bioavailability • metabolism • pharmacokinetics • elimination half-life • humans

INTRODUCTION

Epidemiologic studies have clearly shown that diets rich in plant foods protect humans against degenerative diseases such as cancer and cardiovascular diseases. Plant foods contain fiber, vitamins, phytosterols, sulfur compounds, carotenoids, and organic acids, which contribute to the health effects, but they also contain a variety of polyphenols, which are increasingly regarded as effective protective agents.

Polyphenols represent a wide variety of compounds, which are divided into several classes, ie, hydroxybenzoic acids, hydroxycinnamic acids, anthocyanins, proanthocyanidins, flavonols, flavones, flavanols, flavanones, isoflavones, stilbenes, and lignans. The chemical structures and the food contents of the various polyphenols have been reviewed elsewhere (1). One of the main objectives of bioavailability studies is to determine, among the hundreds of dietary polyphenols, which are better absorbed and which lead to the formation of active metabolites.

Many researchers have investigated the kinetics and extent of polyphenol absorption by measuring plasma concentrations and/or urinary excretion among adults after the ingestion of a single dose of polyphenol, provided as pure compound, plant extract, or whole food/beverage. We have reviewed 97 studies of various classes of polyphenols, namely, anthocyanins, flavonols, flavanones, flavanol monomers, proanthocyanidins, isoflavones, hydroxycinnamic acids, and hydroxybenzoic acids. We have compiled the data from the most relevant studies, ie, those using well-described polyphenol sources and accurate methods of analysis, to calculate mean values for several bioavailability measures, including the maximal plasma concentration (Cmax), time to reach Cmax, area under the plasma concentration-time curve, elimination half-life, and relative urinary excretion. The results clearly show wide variability in the bioavailability of the different polyphenols.

ANTHOCYANINS

Anthocyanins are present in very large amounts in some diets. Servings of 200 g of aubergine or black grapes can provide up to 1500 mg anthocyanins and servings of 100 g of berries up to 500 mg. Therefore, an intake of several hundred milligrams would not be considered exceptional. The mean dietary intake in Finland has been estimated to be 82 mg/d, with the main sources being berries, red wine, juices, and the coloring agent E163 (M Heinonen, personal communication, 2001).

The results of a literature survey on the bioavailability of anthocyanins among humans are presented in Table 1Go. Single doses of 150 mg to 2 g total anthocyanins were given to the volunteers, generally in the form of berries, berry extracts, or concentrates. After such intakes, concentrations of anthocyanins measured in plasma were very low, on the order of 10–50 nmol/L.The mean time to reach Cmax was 1.5 h (range: 0.75–4 h) for plasma and 2.5 h for urine. Most studies reported low relative urinary excretions, ranging from 0.004% to 0.1% of the intake, although Lapidot et al (11) and Felgines et al (14) measured higher levels of anthocyanin excretion (up to 5%) after red wine or strawberry consumption. The time course of absorption was consistent with absorption in the stomach, as described for animals (15, 16). The most striking features of the survey were thus that anthocyanins are very rapidly absorbed and eliminated and that they are absorbed with poor efficiency.


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  		TABLE 1. Bioavailability studies of anthocyanins or anthocyanin-containing foods1

 
Although anthocyanin bioavailability appears low, it could have been underestimated, for 2 main reasons, ie, some important metabolites might have been ignored or the methods used might need to be optimized for the analysis of anthocyanin metabolites. It is well known that different chemical forms of anthocyanins are present in equilibrium, depending on the pH. In most studies, analyses were performed with ultraviolet-visible light detection, on the basis of complete conversion of all of the chemical forms of anthocyanins into a colored flavylium cation with acidification. However, it is possible that some forms existing at neutral pH would not be converted into the flavylium form, because of putative binding to or chemical reactions with other components of the plasma or urine, for example. It would be very useful to have labeled anthocyanins for identification of all of the metabolites generated from these polyphenols.

With our current knowledge, there seem to be important differences in the metabolism of anthocyanins, compared with other polyphenols. Whereas flavonoids are generally recovered in plasma and urine as glucuronidated and/or sulfated derivatives, with no or only trace amounts of native forms, unchanged glycosides were the only metabolites identified for anthocyanins in most studies. However, glucuronides and sulfates of anthocyanins were recently identified in human urine with HPLC-mass spectrometry/mass spectrometry analyses (6, 14). In the study conducted by Felgines et al (14), monoglucuronides accounted for >80% of the total metabolites when analyses were performed immediately after urine collection. The authors also showed that all of the metabolites of the strawberry anthocyanins, except for the native glucoside, were very unstable and were extensively degraded when acidified urine samples were frozen for storage. This probably explains why such metabolites were not observed in previous studies. Therefore, it seems crucial to reconsider anthocyanin bioavailability, with methods that allow preservation of all of the metabolites in frozen samples.

Other metabolites that have not yet been considered but could contribute to the biological effects of anthocyanins are the metabolites produced by the intestinal microflora. However, studies performed in the 1970s showed that degradation of anthocyanins by the microflora occurs to a much more limited extent than with other flavonoids (17). Protocatechuic acid was identified as an abundant metabolite of cyanidin-3-O-glucoside in rats, but it was also formed in vitro with simple incubation of cyanidin with rat plasma in the absence of colonic bacteria (18). Identification of all of the microbial metabolites in humans should be reinvestigated with pure anthocyanins and not only berry extracts, which contain other polyphenols as well as anthocyanins.

FLAVONOLS

Flavonols, especially quercetin, have been extensively studied, mainly because they are widely distributed in dietary plants. However, their content in the diet is generally quite low. The daily intake of flavonols has been estimated as only 20–35 mg/d (19–22).

Twenty years after Gugler et al (23, 24) failed to find quercetin in plasma or urine from volunteers challenged with 4 g pure aglycone, the team of Hollman et al (23, 24) showed that quercetin was indeed absorbed in humans. They demonstrated that glucosides of quercetin were more efficiently absorbed than quercetin itself, whereas the rhamnoglucoside (rutin) was less efficiently and less rapidly absorbed (Table 2Go). This difference in absorption rates was confirmed by others (33, 34). When pure compounds were given, the bioavailability of rutin was ~20% that of quercetin glucosides, on the basis of area under the plasma concentration-time curve values and relative urinary excretions (30, 34). The biochemical explanation for the better absorption of quercetin glucosides has been discussed elsewhere (1). It is clear that, for quercetin, bioavailability differs among food sources, depending on the type of glycosides they contain. For example, onions, which contain glucosides, are better sources of bioavailable quercetin than are apples and tea, which contain rutin and other glycosides.


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  		TABLE 2. Bioavailability studies of flavonols or flavanol-containing foods1

 
The presence of intact glycosides of quercetin in plasma was debated a few years ago, but it is now accepted that such compounds are absent from plasma after nutritional doses (34, 37–40). Quercetin is not present as an aglycone and occurs only in conjugated forms. Generally, ~20–40% of quercetin is methylated in the 3'-position, yielding isorhamnetin (31, 34, 38). The exact nature of the metabolites present in plasma after the ingestion of onions was determined by Day et al (38). They identified quercetin-3'-O-glucuronide, 3'-O-methylquercetin-3-O-glucu-ronide, and quercetin-3'-O-sulfate as the major conjugates.

Some phenolic and aromatic acids can also be produced from flavonols by the microflora. Quercetin degradation produces mainly 3,4-dihydroxyphenylacetic, 3-methoxy-4-hydroxyphenylacetic (homovanillic acid), and 3-hydroxyphenylacetic acid (17, 41–43). The total urinary excretion of microbial metabolites accounted for as much as 50% of the ingested dose among volunteers challenged with 75 mg rutin (44).

One characteristic feature of quercetin bioavailability is that the elimination of quercetin metabolites is quite slow, with reported half-lives ranging from 11 to 28 h. This could favor accumulation in plasma with repeated intakes. A few authors investigated the bioavailability of quercetin after several days or weeks of supplementation. Baseline quercetin concentrations, measured after overnight fasting, were generally ~50–80 nmol/L, and values were even lower when a low-polyphenol diet was given to the volunteers before a test meal (45, 46). The baseline concentration slightly increased (165 nmol/L) after 6-wk supplementation with 500 mg/d pure rutin (32). The increase was more pronounced in 2 other studies; plasma concentrations reached 1.5 µmol/L after 28 d of supplementation with a high dose of quercetin (>1 g/d) (47) and 0.63 µmol/L after supplementation with 80 mg/d quercetin equivalents for 1 wk (37). It should be noted that very high interindividual variability was observed in the latter study and in others (27, 34, 37). Some individuals could be better absorbers than others, possibly because of particular polymorphisms for intestinal enzymes or transporters. Quantitative data are still lacking for other flavonols and flavones.

FLAVANONES

Flavanones represent a small group of compounds, including glycosides of hesperetin present in oranges and glycosides of naringenin present in grapefruit. The bioavailability of the glycosides of eriodictyol, present in lemons, has never been studied in humans. The Cmax values for flavanone metabolites were measured ~5 h after the ingestion of citrus fruits (Table 3Go). This is the time required for hydrolysis of the rhamnoglycosides hesperidin, naringin, and narirutin by the microflora, before absorption of the released aglycones in the colon. Aglycones are absorbed more rapidly; Bugianesi et al (50) showed that Cmax was reached as early as 2 h after the ingestion of tomato paste, which contains naringenin aglycone. However, natural foods rarely contain significant amounts of flavanones in the aglycone form.


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  		TABLE 3. Bioavailability studies of flavanones or flavanone-containing foods1

 
Plasma metabolites of flavanones have not yet been identified. Monoglucuronides of hesperetin were shown to be the major forms present in plasma after ingestion of orange juice, but the positions of glucuronidation are still not known (48). Microbial metabolites such as p-hydroxyphenylpropionic acid, p-coumaric acid, p-hydroxybenzoic acid, and phenylpropionic acid were produced with in vitro incubation of naringenin with human microflora (17, 55, 56). They were also detected in rat urine (57). The same types of microbial metabolites were detected for hesperetin (58, 59). Therefore, microbial metabolites may also be present in human plasma.

The total urinary excretion of conjugated flavanones accounted for 8.6% of the intake for hesperidin and 8.8% for naringin (Table 3Go). Plasma concentrations reached 1.3–2.2 µmol/L hesperetin metabolites with an intake of 130–220 mg given as orange juice (48, 49) and up to 6 µmol/L naringenin metabolites with 200 mg ingested as grapefruit juice (49). However, data are still scarce, with only 3 studies having investigated the bioavailability of flavanones in plasma.

CATECHINS

The daily intake of catechin and proanthocyanidin dimers and trimers has been estimated to be 18–50 mg/d, with the main sources being tea, chocolate, apples, pears, grapes, and red wine (60, 61). Although they are present in many fruits and in red wine, the bioavailability of catechins has been studied mainly after ingestion of cocoa or tea (Table 4Go).


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  		TABLE 4. Bioavailability studies of flavanols or flavanol-containing foods1

 
Bioavailability differs markedly among catechins. By giving pure catechins individually, van Amelsvoort et al (78) demonstrated that galloylation of catechins reduces their absorption. They found that only epigallocatechin was methylated and that 4'-O-methyl-epigallocatechin accounted for 30–40% of the total metabolites of epigallocatechin. In another study, the 4'-O-methyl-epigallocatechin concentration was 5 times higher than that of epigallocatechin in plasma and 3 times higher than that in urine (84). Meng et al (74) recently showed that epigallocatechin gallate (EGCG) was also methylated into 4',4"-di-O-methyl-EGCG. The concentration of this metabolite was ~15% that of EGCG in human plasma. Catechin was also methylated but preferentially in the 3-position (68). Only unchanged catechins were measured in most studies, whereas the methylated metabolites were not analyzed. Therefore, the mean bioavailability parameters calculated in this review for catechins are probably underestimated.

EGCG is the only known polyphenol present in plasma in large proportion (77–90%) in a free form (73–76). The other catechins are highly conjugated with glucuronic acid and/or sulfate groups. The exact nature of the major circulating metabolites of epicatechin has been elucidated, ie, epicatechin-3'-O-glucuronide, 4'-O-methylepicatechin-3'-O-glucuronide, 4'-O-methylepicatechin-5- or 7-O-glucuronide, and the aglycones epicatechin and 4'-O-methylepicatechin (89).

Microbial metabolites, namely, 5-(3',4',5'-trihydroxyphenyl)valerolactone, 5-(3',4'-dihydroxyphenyl)valerolactone, and 5-(3',5'-dihydroxyphenyl)valerolactone, mostly in conjugated forms, were also identified in plasma and urine of volunteers after ingestion of green tea (74). These metabolites accounted for 6–39% of the ingested epigallocatechin and epicatechin, 8–25 times the levels measured for the unchanged compounds (90). Because they appear later than catechins in plasma and have long half-lives, these compounds could prolong the actions of catechins (75). They probably exert some interesting antioxidant activity, because of their di-/trihydroxyphenyl groups.

Catechins are rapidly eliminated. Galloylated catechins were never recovered in urine (75, 76, 78). This is explained not by degalloylation, which has been shown to be a minor process in humans, but rather by preferential excretion of these compounds in bile (78). Extensive biliary excretion of EGCG was previously reported in rats (91).

PROANTHOCYANIDINS

Because of the lack of accurate data on the proanthocyanidin contents of foods, we are not yet able to provide a good estimation of the mean daily intake of these compounds. However, nearly one-half of 88 tested foods derived from plants were found to be dietary sources of proanthocyanidins, which suggests that these are among the most abundant polyphenols in our diet (92).

Polymeric proanthocyanidins are not absorbed as such. The detection of proanthocyanidin dimers B1 and B2 in human plasma was reported in only 2 studies (62, 93) (Table 5Go). The absorption of these dimers was minor, ~100-fold lower than that of the flavanol monomers in the study by Holt et al (62). In vitro and animal studies confirmed that polymerization greatly impairs intestinal absorption (94–96).


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  		TABLE 5. Bioavailability studies of proanthocyanidins or proanthocyanidin-containing foods1

 
However, health effects of proanthocyanidins may not require efficient absorption through the gut. Indeed, these compounds may have direct effects on the intestinal mucosa and protect it against oxidative stress or the actions of carcinogens. In addition, the consumption of proanthocyanidin-rich foods, such as cocoa, red wine, or grape seed extracts, has been shown to increase the plasma antioxidant capacity, to have positive effects on vascular function, and to reduce platelet activity in humans (97). These procyanidin-rich sources always contain 5–25% monomers or other polyphenols, which leaves doubts about whether proanthocyanidins are actually the active compounds in these sources. If they are, then they may have effects through interactions with other components, such as lipids or iron, in the gut.

Biological effects may be attributable not to direct actions of proanthocyanidins themselves but to actions of some of their metabolites that can be more readily absorbed. On the basis of in vitro experiments, Spencer et al (98) suggested that polymers could be degraded into monomers during their transit in the stomach. However, Rios et al (99) clearly demonstrated that this does not occur in humans, probably because the food bolus has a buffering effect, making the acidic conditions milder than required for proanthocyanidin hydrolysis.

Proanthocyanidins are degraded into various aromatic acids by the microflora. The incubation of purified, 14C-labeled, proanthocyanidin oligomers with human colonic microflora led to the formation of m-hydroxyphenylpropionic acid, m-hydroxyphenylacetic acid, and their p-hydroxy isomers, m-hydroxyphenylvaleric acid, phenylpropionic acid, phenylacetic acid, and benzoic acid (100). Some of these compounds, namely, m-hydroxyphenylpropionic acid and m-hydroxyphenylacetic acid, as well as m-hydroxybenzoic acid, were shown to increase in human urine after consumption of procyanidin-rich chocolate (101). However, the microbial metabolism of proanthocyanidins has never been studied in humans after consumption of purified proanthocyanidin polymers. By feeding rats with purified catechin, dimer B3, trimer C2, or procyanidin polymers, Gonthier et al (102) showed that the extent of degradation into aromatic acids decreased as the degree of polymerization increased; it was 21 times lower for polymers than for the catechin monomer, probably because of the antimicrobial properties and protein-binding capacity frequently described for proanthocyanidins. Therefore, the quantitative importance of the degradation of proanthocyanidins into microbial metabolites must be further evaluated in humans.

ISOFLAVONES

Isoflavones are provided only by soybean-derived products. They can be present as aglycones or glycosides, depending on the soy preparation. Some authors investigated the differences in bioavailability between aglycones and glycosides by using pure molecules. Contradictory results have been obtained (Table 6Go). Setchell et al (112) found greater bioavailability of glucosides, as measured from the areas under the plasma concentration-time curves. Izumi et al (110) found greater bioavailability of aglycones, on the basis of Cmax, but they did not measure isoflavone concentrations between 6 and 24 h, whereas Setchell et al (112) reported that the mean time to reach Cmax was prolonged to 9 h after glycoside ingestion. Two other studies found no significant differences in the absorption efficiency for aglycones and glycosides (117, 118).


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  		TABLE 6. Bioavailability studies of isoflavones or isoflavone-containing foods1

 
In contrast, equol production was significantly higher after ingestion of daidzin than after ingestion of daidzein (112, 117). Equol is a bacterial metabolite that has been shown to be more estrogenic than its precursor daidzein in many in vitro studies and in animal models (119). There is great interindividual variability in the capacity to produce equol, and only 30-40% of the Western population are "equol producers." Equol producers may gain more benefits from soy consumption than do nonproducers (119, 120). Therefore, it would be interesting to find a way to make nonproducers become producers. To date, no clear correlations between dietary habits or microflora composition and the capacity to produce equol have been reported. It would be interesting to separate volunteers into equol producers and nonproducers in future intervention studies designed to investigate the effects of soy isoflavones. Cmax values for equol were measured 12–24 h after isoflavone ingestion (112, 117).

It has long been thought that the greater urinary excretion of daidzein reflects greater bioavailability of this isoflavone, compared with genistein (103). The explanation is that a greater fraction of genistein is eliminated in bile, as observed in rats (121). Plasma kinetic curves often showed a first peak followed ~3 h later by a second peak, reflecting enterohepatic cycling (112, 117). By using 13C-labeled daidzein and genistein, Setchell et al (116) recently showed that the systemic bioavailability and Cmax were significantly higher for genistein than for daidzein. The limited data for glycitein indicate greater bioavailability than for the other isoflavones (107, 114).

The nature of isoflavone metabolites was the same after glycoside or aglycone ingestion. Glycosides are hydrolyzed before absorption and are not recovered as such in plasma (122). Aglycones have been recovered in small proportions, generally <5% of the total metabolites (111–113, 123). The main metabolites are 7-O-glucuronides and 4'-O-glucuronides, with small proportions of sulfate esters (111, 123, 124). Additional metabolites have been identified in human plasma or urine, including dihydrodaidzein, dihydrogenistein, dihydroequol, O-desmethylangolensin, and 6-hydroxy-O-desmethylangolensin (125–127).

Elimination of isoflavones is quite slow, with half-life values of 6–8 h (Table 6Go). After ingestion of daidzein or genistein at 0.4 or 0.8 mg/kg body weight, baseline concentrations of isoflavones in plasma were regained only after ~48 h (116). Plasma concentrations should therefore increase with repeated ingestion of soy products. However, Lu et al (128) reported that relative urinary excretion of isoflavones and elimination half-lives progressively decreased during 4 wk of daily soymilk ingestion. Lampe et al (129) did not observe any effect on urinary excretion of 1-mo supplementation with isoflavones.

Another point worth noting is the evidence that high concentrations of isoflavones can be found in breast tissue of premenopausal women and in prostate glands of men (130–132). These are the only available data on polyphenol concentrations in tissues.

HYDROXYCINNAMIC ACIDS

Intake of chlorogenic acid varies widely but may be very high, up to 800 mg/d among coffee drinkers (133, 134). Nevertheless, very few studies have addressed the bioavailability of this hydroxycinnamic acid, in comparison with other polyphenols (Table 7Go).


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  		TABLE 7. Bioavailability studies of hydroxycinnamic acids or hydroxycinnamic acid-containing foods1

 
Olthof et al (138) showed that the esterification of caffeic acid, as in chlorogenic acid, markedly reduced its absorption. This was also observed in rats (145, 146). In fact, the absorption of chlorogenic acid occurs mainly in the colon, after hydrolysis by microbial esterases. It is not clear whether chlorogenic acid is present, as such or in a conjugated form, in human plasma. Nardini et al (135) found only caffeic acid in plasma after the ingestion of coffee. We observed, however, that the preparation of ß-glucuronidase from Helix pomatia that is generally used to hydrolyze samples also contains esterases that are able to degrade chlorogenic acid into caffeic acid. Therefore, the possibility that chlorogenic acid is present in plasma but is hydrolyzed during sample treatment cannot be excluded. Intact chlorogenic acid has been detected at low concentrations in nonhydrolyzed urine samples (138, 147). Metabolites other than caffeic acid have been identified after ingestion of chlorogenic or caffeic acid, namely, ferulic acid, isoferulic acid, dihydroferulic acid, vanillic acid, 3,4-dihydroxyphenylpropionic acid, 3-hydroxyhippuric acid, and hippuric acid (139, 140, 147). Their quantitative importance remains to be investigated.

Ferulic acid is another abundant hydroxycinnamic acid. When present in free form in tomatoes or beer, it is efficiently absorbed (143, 144). However, ferulic acid is also the main polyphenol present in cereals, in which it is esterified to the arabinoxylans of the grain cell walls. This binding has been reported to hamper the absorption of ferulic acid in rats (148, 149). In humans, Kern et al (142) measured the urinary excretion and plasma concentrations of ferulic acid metabolites after ingestion of breakfast cereals. They deduced from the kinetic data that absorption of ferulic acid from cereals takes place mainly in the small intestine, from the soluble fraction present in cereals. Only a minor amount of ferulic acid linked to arabinoxylans was absorbed after hydrolysis in the large intestine.

HYDROXYBENZOIC ACIDS

Very little is known about the absorption and metabolism of hydroxybenzoic acids (150). Their limited distribution in food has resulted in limited interest by nutritionists. However, the few studies addressing the bioavailability of gallic acid in humans revealed that this compound is extremely well absorbed, compared with other polyphenols (Table 8Go). Plasma concentrations of free and glucuronidated forms of gallic acid and its main metabolite 4-O-methylgallic acid reached 4 µmol/L after ingestion of 50 mg pure gallic acid. Such intake is not inconceivable, because red wine usually contains 10–60 mg/L gallic acid. However, gallic acid exists in different forms in fruits, nuts, tea, and red wine, ie, the free form, esterified to glucose (as in hydrolyzable tannins), or esterified to catechins or proanthocyanidins (92, 154). It would be interesting to compare the bioavailability of the different forms of gallic acid.


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  		TABLE 8. Bioavailability studies of gallic acid or gallic acid-containing foods1

 
COMPARATIVE BIOAVAILABILITY OF POLYPHENOLS

Mean values for Cmax, time to reach Cmax, area under the plasma concentration-time curve, elimination half-life, and relative urinary excretion (related to the ingested dose) were calculated for the different polyphenols (Table 9Go), on the basis of the data compiled in Tables 1Go–8Go. Only data from studies using a single dose of a well-characterized polyphenol source were taken into account. To facilitate comparisons between polyphenols, data were converted to correspond to the same supply of polyphenols, a single 50-mg dose of aglycone equivalent. For this, we assumed that the bioavailability parameters increase linearly with the dose, which has been demonstrated in humans only for EGCG (73). When several doses were investigated in the same study, only a mean value for the whole study was considered.


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  		TABLE 9. Compilation of pharmacokinetic data from 97 bioavailability studies1

 
The most striking result of this survey was that gallic acid is far better absorbed than the other polyphenols. The Cmax values for its metabolites reached 4 µmol/L with a 50-mg intake, and the relative urinary excretion was 38%. Next are isoflavones, which are the most well-absorbed flavonoids, with Cmax values of ~2 µmol/L after a 50-mg intake and mean relative urinary excretions of 42% for daidzin and 15.6% for genistin. Proanthocyanidins and anthocyanins are very poorly absorbed but, in the case of anthocyanins, all of the metabolites might not have been identified, resulting in underestimation of their bioavailability. Values for catechins are certainly underestimated, because methylated metabolites were not taken into account in some studies. Data are still scarce for hydroxycinnamic acids, and the calculated mean values are probably not very reliable.

The mean area under the plasma concentration-time curve, Cmax, and urinary excretion values clearly show the lower absorption of rutin, compared with quercetin glucosides. Another observation is that galloylation of epigallocatechin markedly reduces its absorption. Gallic acid, quercetin glucosides, catechins, free hydroxycinnamic acids, and anthocyanins, which are absorbed in the small intestine or the stomach, reached Cmax at ~1.5 h, whereas rutin and the flavanones hesperidin and naringin, which are absorbed after release of the aglycones by the microflora, reached Cmax at ~5.5 h. The mean time to reach Cmax for chlorogenic acid is surprising, because this compound also must be hydrolyzed by the microflora before absorption. In the sole study considered, however, chlorogenic acid was provided as a liquid (coffee) to fasted volunteers, which might have accelerated the absorption kinetics.

Relative urinary excretion is currently used to estimate the minimal absorption rate but, when polyphenols are highly excreted in bile, as for EGCG and genistein, absorption is underestimated. For most polyphenols, the urinary excretion values were consistent with the plasma kinetic data. Values ranged from 0.3% to 43% of the intake, which demonstrates the great variability in the bioavailability of the different polyphenols.

With respect to the elimination half-lives, it appears that catechins, gallic acid, and flavanones have no chance to accumulate in plasma with repeated ingestion. Some of their metabolites may have longer half-lives, however, and quercetin, with a longer half-life, could accumulate in plasma with repeated ingestion.

Extensive variability was observed among the studies. Ten-fold variations in the Cmax values were observed for most compounds. Several factors may explain the variability, such as the food matrix or background diet. Interindividual variations are also important, and some people might have different levels of metabolizing enzymes or transporters, enabling more efficient absorption of polyphenols.

It is important to realize that the mode of calculation and representation used in this review does not take into account the mean dietary intake of each polyphenol. For example, even if isoflavones are efficiently absorbed, they are usually not the major circulating polyphenols in Western populations, because the isoflavone intake is far lower than 50 mg/d for these populations. In contrast, a single glass of orange juice easily provides 50 mg hesperidin.

CONCLUSIONS

Bioavailability varies widely among polyphenols and, for some of compounds, among dietary sources, depending on the forms they contain. The plasma concentrations of total metabolites range from 0 to 4 µmol/L with an intake of 50 mg aglycone equivalents. The polyphenols that are most well absorbed in humans are isoflavones and gallic acid, followed by catechins, flavanones, and quercetin glucosides, with different kinetics. The least well-absorbed polyphenols are the proanthocyanidins, the galloylated tea catechins, and the anthocyanins. Data for other polyphenols are still too limited. The plasma kinetics also differ among polyphenol classes, with Cmax being reached after ~1.5 h or ~5.5 h, depending on the site of intestinal absorption. This information should be useful for the design and interpretation of intervention studies investigating the health effects of polyphenols.

REFERENCES

  1. Manach C, Scalbert A, Morand C, Rémésy C, Jimenez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004;79:727–47.[Abstract/Free Full Text]
  2. Nielsen IL, Dragsted LO, Ravn-Haren G, Freese R, Rasmussen SE. Absorption and excretion of black currant anthocyanins in humans and Watanabe heritable hyperlipidemic rabbits. J Agric Food Chem 2003;51:2813–20.[Medline]
  3. Rechner AR, Kuhnle G, Hu H, et al. The metabolism of dietary polyphenols and the relevance to circulating levels of conjugated metabolites. Free Radic Res 2002;36:1229–41.[Medline]
  4. Netzel M, Strass G, Janssen M, Bitsch I, Bitsch R. Bioactive anthocyanins detected in human urine after ingestion of blackcurrant juice. J Environ Pathol Toxicol Oncol 2001;20:89–95.[Medline]
  5. Matsumoto H, Inaba H, Kishi M, Tominaga S, Hirayama M, Tsuda T. Orally administered delphinidin 3-rutinoside and cyanidin 3-rutinoside are directly absorbed in rats and humans and appear in the blood as the intact forms. J Agric Food Chem 2001;49:1546–51.[Medline]
  6. Wu X, Cao G, Prior RL. Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry. J Nutr 2002;132:1865–71.[Abstract/Free Full Text]
  7. Cao G, Muccitelli HU, Sanchez-Moreno C, Prior RL. Anthocyanins are absorbed in glycated forms in elderly women: a pharmacokinetic study. Am J Clin Nutr 2001;73:920–6.[Abstract/Free Full Text]
  8. Mulleder U, Murkovic M, Pfannhauser W. Urinary excretion of cyanidin glycosides. J Biochem Biophys Methods 2002;53:61–6.[Medline]
  9. Murkovic M, Mülleder U, Adam U, Pfannhauser W. Detection of anthocyanins from elderberry juice in human urine. J Sci Food Agric 2001;81:934–7.
  10. Mazza G, Kay CD, Cottrell T, Holub BJ. Absorption of anthocyanins from blueberries and serum antioxidant status in human subjects. J Agric Food Chem 2002;50:7731–7.[Medline]
  11. Lapidot T, Harel S, Granit R, Kanner J. Bioavailability of red wine anthocyanins as detected in human urine. J Agric Food Chem 1998;46:4297–302.
  12. Bub A, Watzl B, Heeb D, Rechkemmer G, Briviba K. Malvidin-3-glucoside bioavailability in humans after ingestion of red wine, dealcoholized red wine and red grape juice. Eur J Nutr 2001;40:113–20.[Medline]
  13. Miyazawa T, Nakagawa K, Kudo M, Muraishi K, Someya K. Direct intestinal absorption of red fruit anthocyanins, cyanidin-3-glucoside and cyanidin-3,5-diglucoside, into rats and humans. J Agric Food Chem 1999;47:1083–91.[Medline]
  14. Felgines C, Talavera S, Gonthier MP, et al. Strawberry anthocyanins are recovered in urine as glucuro- and sulfoconjugates in humans. J Nutr 2003;133:1296–301.[Abstract/Free Full Text]
  15. Talavera S, Felgines C, Texier O, Besson C, Lamaison JL, Remesy C. Anthocyanins are efficiently absorbed from the stomach in anesthetized rats. J Nutr 2003;133:4178–82.[Abstract/Free Full Text]
  16. Passamonti S, Vrhovsek U, Vanzo A, Mattivi F. The stomach as a site for anthocyanins absorption from food. FEBS Lett 2003;544:210–3.[Medline]
  17. Scheline RR. CRC handbook of mammalian metabolism of plant compounds. Boca Raton, FL: CRC Press, 1991.
  18. Tsuda T, Horio F, Osawa T. Absorption and metabolism of cyanidin 3-O-ß-D-glucoside in rats. FEBS Lett 1999;449:179–82.[Medline]
  19. Justesen U, Knuthsen P, Leth T. Determination of plant polyphenols in Danish foodstuffs by HPLC-UV and LC-MS detection. Cancer Lett 1997;114:165–7.[Medline]
  20. Hertog MGL, Hollman PCH, Katan MB, Kromhout D. Intake of potentially anticarcinogenic flavonoids and their determinants in adults in the Netherlands. Nutr Cancer 20:21–9, 1993.[Medline]
  21. Pietta P, Simonetti P, Roggi C, et al. Dietary flavonoids and oxidative stress. In: Kumpulainen JT, Salonen JT, eds. Natural antioxidants and food quality in atherosclerosis and cancer prevention. London: Royal Society of Chemistry, 1996:249–55.
  22. Sampson L, Rimm E, Hollman PC, de Vries JH, Katan MB. Flavonol and flavone intakes in US health professionals. J Am Diet Assoc 2002;102:1414–20.[Medline]
  23. Gugler R, Leschik M, Dengler HJ. Disposition of quercetin in man after single oral and intravenous doses. Eur J Clin Pharmacol 1975;9:229–34.[Medline]
  24. Hollman PCH, Devries JHM, Vanleeuwen SD, Mengelers MJB, Katan MB. Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am J Clin Nutr 1995;62:1276–82.[Abstract/Free Full Text]
  25. Hollman PCH, Vandergaag M, Mengelers MJB, Vantrijp JMP, Devries JH, Katan MB. Absorption and disposition kinetics of the dietary antioxidant quercetin in man. Free Radic Biol Med 1996;21:703–7.[Medline]
  26. Hollman PCH, van Trijp JMP, Buysman MNCP, et al. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett 1997;418:152–6.[Medline]
  27. Manach C, Morand C, Crespy V, et al. Quercetin is recovered in human plasma as conjugated derivatives which retain antioxidant properties. FEBS Lett 1998;426:331–6.[Medline]
  28. Aziz AA, Edwards CA, Lean MEJ, Crozier A. Absorption and excretion of conjugated flavonols, including quercetin-4'-O-ß-glucoside and isorhamnetin-4'-O-ß-glucoside by human volunteers after the consumption of onions. Free Radic Res 1998;29:257–69.[Medline]
  29. McAnlis GT, McEneny J, Pearce J, Young IS. Absorption and antioxidant effects of quercetin from onions, in man. Eur J Clin Nutr 1999;53:92–6.[Medline]
  30. Hollman PC, Bijsman MN, van Gameren Y, Cnossen EP, de Vries JH, Katan MB. The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radic Res 1999;31:569–73.[Medline]
  31. Olthof MR, Hollman PCH, Vree TB, Katan MB. Bioavailabilities of quercetin-3-glucoside and quercetin-4'-glucoside do not differ in humans. J Nutr 2000;130:1200–3.[Abstract/Free Full Text]
  32. Boyle SP, Dobson VL, Duthie SJ, Hinselwood DC, Kyle JAM, Collins AR. Bioavailability and efficiency of rutin as an antioxidant: a human supplementation study. Eur J Clin Nutr 2000;54:774–82.[Medline]
  33. Erlund I, Kosonen T, Alfthan G, et al. Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur J Clin Pharmacol 2000;56:545–53.[Medline]
  34. Graefe EU, Wittig J, Mueller S, et al. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J Clin Pharmacol 2001;41:492–9.[Abstract]
  35. DuPont MS, Bennett RN, Mellon FA, Williamson G. Polyphenols from alcoholic apple cider are absorbed, metabolized and excreted by humans. J Nutr 2002;132:172–5.[Abstract/Free Full Text]
  36. Goldberg DM, Yan J, Soleas GJ. Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin Biochem 2003;36:79–87.[Medline]
  37. Moon JH, Nakata R, Oshima S, Inakuma T, Terao J. Accumulation of quercetin conjugates in blood plasma after the short-term ingestion of onion by women. Am J Physiol Regul Integr Comp Physiol 2000;279:R461–7.[Abstract/Free Full Text]
  38. Day AJ, Mellon F, Barron D, Sarrazin G, Morgan MR, Williamson G. Human metabolism of dietary flavonoids: identification of plasma metabolites of quercetin. Free Radic Res 2001;35:941–52.[Medline]
  39. Wittig J, Herderich M, Graefe EU, Veit M. Identification of quercetin glucuronides in human plasma by high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 2001;753:237–43.[Medline]
  40. Sesink AL, O'Leary KA, Hollman PC. Quercetin glucuronides but not glucosides are present in human plasma after consumption of quercetin-3-glucoside or quercetin-4'-glucoside. J Nutr 2001;131:1938–41.[Abstract/Free Full Text]
  41. Booth AN, Deeds F, Jones FT, Murray CW. The metabolic fate of rutin and quercetin in the animal body. J Biol Chem 1956;223:251–7.[Free Full Text]
  42. Baba S, Furuta T, Horie M, Nakagawa H. Studies on drug metabolism by use of isotopes. XXVI. Determination of urinary metabolites of rutin in humans. J Pharm Sci 1981;70:780–2.[Medline]
  43. Aura AM, O'Leary KA, Williamson G, et al. Quercetin derivatives are deconjugated and converted to hydroxyphenylacetic acids but not methylated by human fecal flora in vitro. J Agric Food Chem 2002;50:1725–30.[Medline]
  44. Sawai Y, Kohsaka K, Nishiyama Y, Ando K. Serum concentrations of rutoside metabolites after oral administration of a rutoside formulation to humans. Arzneim Forsch 1987;37:729–32.[Medline]
  45. Noroozi M, Burns J, Crozier A, Kelly IE, Lean ME. Prediction of dietary flavonol consumption from fasting plasma concentration or urinary excretion. Eur J Clin Nutr 2000;54:143–9.[Medline]
  46. Erlund I, Silaste ML, Alfthan G, Rantala M, Kesaniemi YA, Aro A. Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables. Eur J Clin Nutr 2002;56:891–8.[Medline]
  47. Conquer JA, Maiani G, Azzini E, Raguzzini A, Holub BJ. Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. J Nutr 1998;128:593–7.[Abstract/Free Full Text]
  48. Manach C, Morand C, Gil-Izquierdo A, Bouteloup-Demange C, Remesy C. Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice. Eur J Clin Nutr 2003;57:235–42.[Medline]
  49. Erlund I, Meririnne E, Alfthan G, Aro A. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J Nutr 2001;131:235–41.[Abstract/Free Full Text]
  50. Bugianesi R, Catasta G, Spigno P, D'Uva A, Maiani G. Naringenin from cooked tomato paste is bioavailable in men. J Nutr 2002;132:3349–52.[Abstract/Free Full Text]
  51. Ishii K, Furuta T, Kasuya Y. Mass spectrometric identification and high-performance liquid chromatographic determination of a flavonoid glycoside naringin in human urine. J Agric Food Chem 2000;48:56–9.[Medline]
  52. Ameer B, Weintraub RA, Johnson JV, Yost RA, Rouseff RL. Flavanone absorption after naringin, hesperidin, and citrus administration. Clin Pharmacol Ther 1996;60:34–40.[Medline]
  53. Fuhr U, Kummert AL. The fate of naringin in humans: a key to grapefruit juice-drug interactions? Clin Pharmacol Ther 1995;58:365–73.[Medline]
  54. Lee YS, Reidenberg MM. A method for measuring naringenin in biological fluids and its disposition from grapefruit juice by man. Pharmacology 1998;56:314–7.[Medline]
  55. Griffiths LA, Smith GE. Metabolism of apigenin and related compounds in the rat. Biochem J 1972;128:901–11.[Medline]
  56. Rechner AR, Smith MA, Kuhnle G, et al. Colonic metabolism of dietary polyphenols: influence of structure on microbial fermentation products. Free Radic Biol Med 2004;36:212–25.[Medline]
  57. Felgines C, Texier O, Morand C, et al. Bioavailability of the flavanone naringenin and its glycosides in rats. Am J Physiol Gastrointest Liver Physiol 2000;279:G1148–54.[Abstract/Free Full Text]
  58. Booth AN, Jones FT, De Eds F. Metabolic fate of hesperidin, eriodictyol, homoeriodictyol, and diosmin. J Biol Chem 1958;230:661–8.[Free Full Text]
  59. Honohan T, Hale RL, Brown JP, Wingard RE. Synthesis and metabolic fate of hesperetin-3-14C. J Agric Food Chem 1976;24:906–11.[Medline]
  60. de Pascual-Teresa S. Analisis de taninos condensados en alimentos. (Analysis of condensed tannins in food.) PhD dissentation. Salamanca, Spain: University of Salamanca, 1999:181 (in Spanish).
  61. Arts ICW, vandePutte B, Hollman PCH. Catechin contents of foods commonly consumed in the Netherlands. 1. Fruits, vegetables, staple foods, and processed foods. J Agric Food Chem 2000;48:1746–51.[Medline]
  62. Holt RR, Lazarus SA, Sullards MC, et al. Procyanidin dimer B2 [epicatechin-(4ß-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am J Clin Nutr 2002;76:798–804.[Abstract/Free Full Text]
  63. Rein D, Lotito S, Holt RR, Keen CL, Schmitz HH, Fraga CG. Epicatechin in human plasma: in vivo determination and effect of chocolate consumption on plasma oxidation status. J Nutr 2000;130:2109S–14S.[Abstract/Free Full Text]
  64. Schramm DD, Karim M, Schrader HR, et al. Food effects on the absorption and pharmacokinetics of cocoa flavanols. Life Sci 2003;73:857–69.[Medline]
  65. Baba S, Osakabe N, Yasuda A, et al. Bioavailability of (–)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radic Res 2000;33:635–41.[Medline]
  66. Wang JF, Schramm DD, Holt RR, et al. A dose-response effect from chocolate consumption on plasma epicatechin and oxidative damage. J Nutr 2000;130:2115S–9S.[Abstract/Free Full Text]
  67. Richelle M, Tavazzi I, Enslen M, Offord EA. Plasma kinetics in man of epicatechin from black chocolate. Eur J Clin Nutr 1999;53:22–6.[Medline]
  68. Donovan JL, Bell JR, Kasim-Karakas S, et al. Catechin is present as metabolites in human plasma after consumption of red wine. J Nutr 1999;129:1662–8.[Abstract/Free Full Text]
  69. Bell JRC, Donovan JL, Wong R, et al. (+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine. Am J Clin Nutr 2000;71:103–8.[Abstract/Free Full Text]
  70. Donovan JL, Kasim-Karakas S, German JB, Waterhouse AL. Urinary excretion of catechin metabolites by human subjects after red wine consumption. Br J Nutr 2002;87:31–7.[Medline]
  71. Hackett AM, Griffiths LA, Broillet A, Wermeille M. The metabolism and excretion of (+)-[14C]cyanidanol-3 in man following oral administration. Xenobiotica 1983;13:279–86.[Medline]
  72. Balant L, Burki B, Wermeille M, Golden G. Comparison of some pharmacokinetic parameters of (+)-cyanidanol-3 obtained with specific and non-specific analytical methods. Arzneim Forsch 1979;29:1758–62.[Medline]
  73. Ullmann U, Haller J, Decourt JP, et al. A single ascending dose study of epigallocatechin gallate in healthy volunteers. J Int Med Res 2003;31:88–101.[Medline]
  74. Meng X, Sang S, Zhu N, et al. Identification and characterization of methylated and ring-fission metabolites of tea catechins formed in humans, mice, and rats. Chem Res Toxicol 2002;15:1042–50.[Medline]
  75. Lee MJ, Maliakal P, Chen L, et al. Pharmacokinetics of tea catechins after ingestion of green tea and (–)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol Biomarkers Prev 2002;11:1025–32.[Abstract/Free Full Text]
  76. Chow HHS, Cai Y, Alberts DS, et al. Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomarkers Prev 2001;10:53–8.[Abstract/Free Full Text]
  77. Unno T, Kondo K, Itakura H, Takeo T. Analysis of (–)-epigallocatechin gallate in human serum obtained after ingesting green tea. Biosci Biotechnol Biochem 1996;60:2066–8.[Medline]
  78. van Amelsvoort JM, Van Hof KH, Mathot JN, Mulder TP, Wiersma A, Tijburg LB. Plasma concentrations of individual tea catechins after a single oral dose in humans. Xenobiotica 2001;31:891–901.[Medline]
  79. Nakagawa K, Okuda S, Miyazawa T. Dose-dependent incorporation of tea catechins, (–)-epigallocatechin-3-gallate and (–)-epigallocatechin, into human plasma. Biosci Biotechnol Biochem 1997;61:1981–5.[Medline]
  80. Lee M-J, Wang Z-Y, Li H, et al. Analysis of plasma and urinary tea polyphenols in human subjects. Cancer Epidemiol Biomarkers Prev 1995;4:393–9.[Abstract]
  81. Yang CS, Chen L, Lee MJ, Balentine D, Kuo MC, Schantz SP. Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers. Cancer Epidemiol Biomarkers Prev 1998;7:351–4.[Abstract]
  82. Kimura M, Umegaki K, Kasuya Y, Sugisawa A, Higuchi M. The relation between single/double or repeated tea catechin ingestions and plasma antioxidant activity in humans. Eur J Clin Nutr 2002;56:1186–93.[Medline]
  83. van het Hof KH, Kivits GA, Weststrate JA, Tijburg LB. Bioavailability of catechins from tea: the effect of milk. Eur J Clin Nutr 1998;52:356–9.[Medline]
  84. Meng X, Lee MJ, Li C, et al. Formation and identification of 4'-O-methyl-(–)-epigallocatechin in humans. Drug Metab Dispos 2001;29:789–93.[Abstract/Free Full Text]
  85. Leenen R, Roodenburg AJ, Tijburg LB, Wiseman SA. A single dose of tea with or without milk increases plasma antioxidant activity in humans. Eur J Clin Nutr 2000;54:87–92.[Medline]
  86. van het Hof KH, Wiseman SA, Yang CS, Tijburg LB. Plasma and lipoprotein levels of tea catechins following repeated tea consumption. Proc Soc Exp Biol Med 1999;220:203–9.[Medline]
  87. Pietta PG, Simonetti P, Gardana C, Brusamolino A, Morazzoni P, Bombardelli E. Catechin metabolites after intake of green tea infusions. Biofactors 1998;8:111–8.[Medline]
  88. Warden BA, Smith LS, Beecher GR, Balentine DA, Clevidence BA. Catechins are bioavailable in men and women drinking black tea throughout the day. J Nutr 2001;131:1731–7.[Abstract/Free Full Text]
  89. Natsume M, Osakabe N, Oyama M, et al. Structures of (–)-epicatechin glucuronide identified from plasma and urine after oral ingestion of (–)-epicatechin: differences between human and rat. Free Radic Biol Med 2003;34:840–9.[Medline]
  90. Li C, Lee MJ, Sheng SQ, et al. Structural identification of two metabolites of catechins and their kinetics in human urine and blood after tea ingestion. Chem Res Toxicol 2000;13:177–84.[Medline]
  91. Kohri T, Nanjo F, Suzuki M, et al. Synthesis of (–)-[4-3H]epigallocatechin gallate and its metabolic fate in rats after intravenous administration. J Agric Food Chem 2001;49:1042–8.[Medline]
  92. Gu L, Kelm MA, Hammerstone JF, et al. Screening of foods containing proanthocyanidins and their structural characterization using LC-MS/MS and thiolytic degradation. J Agric Food Chem 2003;51:7513–21.[Medline]
  93. Sano A, Yamakoshi J, Tokutake S, Tobe K, Kubota Y, Kikuchi M. Procyanidin B1 is detected in human serum after intake of proanthocyanidin-rich grape seed extract. Biosci Biotechnol Biochem 2003;67:1140–3.[Medline]
  94. Déprez S, Mila I, Huneau J-F, Tomé D, Scalbert A. Transport of proanthocyanidin dimer, trimer and polymer across monolayers of human intestinal epithelial Caco-2 cells. Antiox Redox Signal 2001;3:957–67.[Medline]
  95. Baba S, Osakabe N, Natsume M, Muto Y, Takizawa T, Terao J. Absorption and urinary excretion of (–)-epicatechin after administration of different levels of cocoa powder or (–)-epicatechin in rats. J Agric Food Chem 2001;49:6050–6.[Medline]
  96. Donovan JL, Manach C, Rios L, Morand C, Scalbert A, Remesy C. Procyanidins are not bioavailable in rats fed a single meal containing a grapeseed extract or the procyanidin dimer B3. Br J Nutr 2002;87:299–306.[Medline]
  97. Williamson G, Manach C. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am J Clin Nutr 2005;81(suppl):243S–55S.
  98. Spencer JP, Chaudry F, Pannala AS, Srai SK, Debnam E, Rice-Evans C. Decomposition of cocoa procyanidins in the gastric milieu. Biochem Biophys Res Commun 2000;272:236–41.[Medline]
  99. Rios LY, Bennett RN, Lazarus SA, Remesy C, Scalbert A, Williamson G. Cocoa procyanidins are stable during gastric transit in humans. Am J Clin Nutr 2002;76:1106–10.[Abstract/Free Full Text]
  100. Déprez S, Brézillon C, Rabot S, et al. Polymeric proanthocyanidins are catabolized by a human colonic microflora into low molecular weight phenolic acids. J Nutr 2000;130:2733–8.[Abstract/Free Full Text]
  101. Rios LY, Gonthier MP, Remesy C, et al. Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects. Am J Clin Nutr 2003;77:912–8.[Abstract/Free Full Text]
  102. Gonthier MP, Donovan JL, Texier O, Felgines C, Remesy C, Scalbert A. Metabolism of dietary procyanidins in rats. Free Radic Biol Med 2003;35:837–44.[Medline]
  103. Xu X, Wang H-J, Murphy PA, Cook L, Hendrich S. Daidzein is a more bioavailable soymilk isoflavone than is genistein in adult women. J Nutr 1994;124:825–32.
  104. Tew BY, Xu X, Wang HJ, Murphy PA, Hendrich S. A diet high in wheat fiber decreases the bioavailability of soybean isoflavones in a single meal fed to women. J Nutr 1996;126:871–7.
  105. King RA, Bursill DB. Plasma and urinary kinetics of the isoflavones daidzein and genistein after a single soy meal in humans. Am J Clin Nutr 1998;67:867–72.[Abstract]
  106. Watanabe S, Yamaguchi M, Sobue T, et al. Pharmacokinetics of soybean isoflavones in plasma, urine and feces of men after ingestion of 60 g baked soybean powder (kinako). J Nutr 1998;128:1710–5.[Abstract/Free Full Text]
  107. Zhang Y, Wang GJ, Song TT, Murphy PA, Hendrich S. Urinary disposition of the soybean isoflavones daidzein, genistein and glycitein differs among humans with moderate fecal isoflavone degradation activity. J Nutr 1999;129:957–62.[Abstract/Free Full Text]
  108. Xu X, Wang HJ, Murphy PA, Hendrich S. Neither background diet nor type of soy food affects short-term isoflavone bioavailability in women. J Nutr 2000;130:798–801.[Abstract/Free Full Text]
  109. Shelnutt SR, Cimino CO, Wiggins PA, Badger TM. Urinary pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein. Cancer Epidemiol Biomarkers Prev 2000;9:413–9.[Abstract/Free Full Text]
  110. Izumi T, Piskula MK, Osawa S, et al. Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. J Nutr 2000;130:1695–9.[Abstract/Free Full Text]
  111. Shelnutt SR, Cimino CO, Wiggins PA, Ronis MJ, Badger TM. Pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein in men and women after consumption of a soy beverage. Am J Clin Nutr 2002;76:588–94.[Abstract/Free Full Text]
  112. Setchell KD, Brown NM, Desai P, et al. Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr 2001;131:1362S–75S.[Abstract/Free Full Text]
  113. Busby MG, Jeffcoat AR, Bloedon LT, et al. Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men. Am J Clin Nutr 2002;75:126–36.[Abstract/Free Full Text]
  114. Bloedon LT, Jeffcoat AR, Lopaczynski W, et al. Safety and pharmacokinetics of purified soy isoflavones: single-dose administration to postmenopausal women. Am J Clin Nutr 2002;76:1126–37.[Abstract/Free Full Text]
  115. Setchell KD, Brown NM, Desai PB, et al. Bioavailability, disposition, and dose-response effects of soy isoflavones when consumed by healthy women at physiologically typical dietary intakes. J Nutr 2003;133:1027–35.[Abstract/Free Full Text]
  116. Setchell KD, Faughnan MS, Avades T, et al. Comparing the pharmacokinetics of daidzein and genistein with the use of 13C-labeled tracers in premenopausal women. Am J Clin Nutr 2003;77:411–9.[Abstract/Free Full Text]
  117. Zubik L, Meydani M. Bioavailability of soybean isoflavones from aglycone and glucoside forms in American women. Am J Clin Nutr 2003;77:1459–65.[Abstract/Free Full Text]
  118. Richelle M, Pridmore-Merten S, Bodenstab S, Enslen M, Offord EA. Hydrolysis of isoflavone glycosides to aglycones by ß-glycosidase does not alter plasma and urine isoflavone pharmacokinetics in postmenopausal women. J Nutr 2002;132:2587–92.[Abstract/Free Full Text]
  119. Setchell KD, Brown NM, Lydeking-Olsen E. The clinical importance of the metabolite equol: a clue to the effectiveness of soy and its isoflavones. J Nutr 2002;132:3577–84.[Abstract/Free Full Text]
  120. Duncan AM, MerzDemlow BE, Xu X, Phipps WR, Kurzer MS. Premenopausal equol excretors show plasma hormone profiles associated with lowered risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2000;9:581–6.[Abstract/Free Full Text]
  121. Sfakianos J, Coward L, Kirk M, Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. J Nutr 1997;127:1260–8.[Abstract/Free Full Text]
  122. Setchell KD, Brown NM, Zimmer-Nechemias L, et al. Evidence for lack of absorption of soy isoflavone glycosides in humans, supporting the crucial role of intestinal metabolism for bioavailability. Am J Clin Nutr 2002;76:447–53.[Abstract/Free Full Text]
  123. Doerge DR, Chang HC, Churchwell MI, Holder CL. Analysis of soy isoflavone conjugation in vitro and in human blood using liquid chromatography-mass spectrometry. Drug Metab Dispos 2000;28:298–307.[Abstract/Free Full Text]
  124. Clarke DB, Lloyd AS, Botting NP, Oldfield MF, Needs PW, Wiseman H. Measurement of intact sulfate and glucuronide phytoestrogen conjugates in human urine using isotope dilution liquid chromatography-tandem mass spectrometry with [13C(3)]isoflavone internal standards. Anal Biochem 2002;309:158–72.[Medline]
  125. Kelly GE, Nelson C, Waring MA, Joannou GE, Reeder AY. Metabolites of dietary (soya) isoflavones in human urine. Clin Chim Acta 1993;223:9–22.[Medline]
  126. Heinonen S, Wahala K, Adlercreutz H. Identification of isoflavone metabolites dihydrodaidzein, dihydrogenistein, 6'-OH-O-DMA, and cis-4-OH-equol in human urine by gas chromatography-mass spectroscopy using authentic reference compounds. Anal Biochem 1999;274:211–9.[Medline]
  127. Rowland I, Faughnan M, Hoey L, Wahala K, Williamson G, Cassidy A. Bioavailability of phyto-oestrogens. Br J Nutr 2003;89:S45–58.
  128. Lu LJ, Lin SN, Grady JJ, Nagamani M, Anderson KE. Altered kinetics and extent of urinary daidzein and genistein excretion in women during chronic soya exposure. Nutr Cancer 1996;26:289–302.[Medline]
  129. Lampe JW, Skor HE, Li S, Wahala K, Howald WN, Chen C. Wheat bran and soy protein feeding do not alter urinary excretion of the isoflavan equol in premenopausal women. J Nutr 2001;131:740–4.[Abstract/Free Full Text]
  130. Maubach J, Bracke ME, Heyerick A, et al. Quantitation of soy-derived phytoestrogens in human breast tissue and biological fluids by high-performance liquid chromatography. J Chromatogr B Anal Technol Biomed Life Sci 2003;784:137–44.[Medline]
  131. Hong SJ, Kim SI, Kwon SM, Lee JR, Chung BC. Comparative study of concentration of isoflavones and lignans in plasma and prostatic tissues of normal control and benign prostatic hyperplasia. Yonsei Med J 2002;43:236–41.[Medline]
  132. Morton MS, Chan PS, Cheng C, et al. Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom. Prostate 1997;32:122–8.[Medline]
  133. Clifford MN. Chlorogenic acids and other cinnamates: nature, occurrence, dietary burden, absorption and metabolism. J Sci Food Agric 2000;80:1033–43.
  134. Radtke J, Linseisen J, Wolfram G. Phenolic acid intake of adults in a Bavarian subgroup of the national food composition survey. Z Ernährungswiss 1998;37:190–7 (in German).[Medline]
  135. Nardini M, Cirillo E, Natella F, Scaccini C. Absorption of phenolic acids in humans after coffee consumption. J Agric Food Chem 2002;50:5735–41.[Medline]
  136. Simonetti P, Gardana C, Pietta P. Plasma levels of caffeic acid and antioxidant status after red wine intake. J Agric Food Chem 2001;49:5964–8.[Medline]
  137. Simonetti P, Gardana C, Pietta P. Caffeic acid as biomarker of red wine intake. Methods Enzymol 2001;335:122–30.[Medline]
  138. Olthof MR, Hollman PCH, Katan MB. Chlorogenic acid and caffeic acid are absorbed in humans. J Nutr 2001;131:66–71.[Abstract/Free Full Text]
  139. Rechner AR, Spencer JP, Kuhnle G, Hahn U, Rice-Evans CA. Novel biomarkers of the metabolism of caffeic acid derivatives in vivo. Free Radic Biol Med 2001;30:1213–22.[Medline]
  140. Rechner AR, Pannala AS, Rice-Evans CA. Caffeic acid derivatives in artichoke extract are metabolised to phenolic acids in vivo. Free Radic Res 2001;35:195–202.[Medline]
  141. Abu-Amsha Caccetta RA, Croft KD, Beilin LJ, Puddey IB. Ingestion of red wine significantly increases plasma phenolic acid concentrations but does not acutely affect ex vivo lipoprotein oxidizability. Am J Clin Nutr 2000;71:67–74.[Abstract/Free Full Text]
  142. Kern SM, Bennett RN, Mellon FA, Kroon PA, Garcia-Conesa MT. Absorption of hydroxycinnamates in humans after high-bran cereal consumption. J Agric Food Chem 2003;51:6050–5.[Medline]
  143. Bourne LC, Rice-Evans C. Bioavailability of ferulic acid. Biochem Biophys Res Commun 1998;253:222–7.[Medline]
  144. Bourne L, Paganga G, Baxter D, Hughes P, Rice-Evans C. Absorption of ferulic acid from low-alcohol beer. Free Radic Res 2000;32:273–80.[Medline]
  145. Azuma K, Ippoushi K, Nakayama M, Ito H, Higashio H, Terao J. Absorption of chlorogenic acid and caffeic acid in rats after oral administration. J Agric Food Chem 2000;48:5496–500.[Medline]
  146. Gonthier MP, Verny MA, Besson C, Remesy C, Scalbert A. Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. J Nutr 2003;133:1853–9.[Abstract/Free Full Text]
  147. Olthof MR, Hollman PC, Buijsman MN, van Amelsvoort JM, Katan MB. Chlorogenic acid, quercetin-3-rutinoside and black tea phenols are extensively metabolized in humans. J Nutr 2003;133:1806–14.[Abstract/Free Full Text]
  148. Adam A, Crespy V, Levrat-Verny MA, et al. The bioavailability of ferulic acid is governed primarily by the food matrix rather than its metabolism in intestine and liver in rats. J Nutr 2002;132:1962–8.[Abstract/Free Full Text]
  149. Zhao Z, Egashira Y, Sanada H. Ferulic acid sugar esters are recovered in rat plasma and urine mainly as the sulfoglucuronide of ferulic acid. J Nutr 2003;133:1355–61.[Abstract/Free Full Text]
  150. Tomas-Barberan FA, Clifford MN. Dietary hydroxybenzoic acid derivatives and their possible role in health protection. J Sci Food Agric 2000;80:1024–32.
  151. Shahrzad S, Bitsch I. Determination of gallic acid and its metabolites in human plasma and urine by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 1998;705:87–95.[Medline]
  152. Shahrzad S, Aoyagi K, Winter A, Koyama A, Bitsch I. Pharmacokinetics of gallic acid and its relative bioavailability from tea in healthy humans. J Nutr 2001;131:1207–10.[Abstract/Free Full Text]
  153. Cartron E, Fouret G, Carbonneau MA, et al. Red-wine beneficial long-term effect on lipids but not on antioxidant characteristics in plasma in a study comparing three types of wine: description of two O-methylated derivatives of gallic acid in humans. Free Radic Res 2003;37:1021–35.[Medline]
  154. Clifford MN, Scalbert A. Ellagitannins: occurrence in food, bioavailability and cancer prevention. J Food Sci Agric 2000;80:1118–25.



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