734 MANACH ET AL absorption was observed with gluco ylation of naringenin and compounds are rapidly absorbed from the small intestine and are nd.the me Glycosylation does not nuence the nature of the n nlan Intact glycosides of quercetin,daidzein, and mplex food (107-110).For fla- nts of acid (12-1).This has also been observed in rats (15,126 com pound noid gly ted by ed().Con of th may spec mechanismof 128).In patients who have undergone colonic ablatio was chlor doses leve have bee shown to be good ligands for this ompound a ir ing o n,an from mos ndition were 100-fold tho of the met lites s ol or acids the nlasm rtions were ma nents using single lavers of Caco-2 cells as a model of hich absoptioninthesmnalintcstm owedthtoattpn oge idin B2 is ver ed in rat free caffeic a d the procya 331s1 16 The poss tha k D a s and dimers in acidic ted by of coffee that nic acid ents However.pur only ofhe bound affeic .Thu a pos sible explan of polyme ation in th of administration us oth stud h intuba tion n the rat study stion of c e by colon and lain the rap However,the dies raise loubt about th minor hs es to The ed charid centra in e mp alent intake of hin (004 rted to he ra com 119).P rbed (up to 25% anthoc from tomatoes in humans(130),its ab ngestion of acid n in the tract or vity phenoli acids produced through bolite esent only 3%ofthe ingested do e when ferulic acid is pro e the ir ing 1131 gents and may be and numer tudy showed that ferloyl este are ghout the reach several hundred per liter ()and partcularly in the intestinal mucos d in the segments of the intestine. intestine (26).However.the roe of ases se ems to studies perform rption oc in the colon aabsorption was observed with glucosylation of naringenin and phlorizin (104, 105). Furthermore, diglucosylation of the lignan secoisolariciresinol decreases its absorption (106). Glycosylation does not influence the nature of the circulating metabolites. Intact glycosides of quercetin, daidzein, and genistein were not recovered in plasma or urine after ingestion as pure compounds or from complex food (107–110). For fla￾vanones, only trace amounts of glycosides have been detected in human urine, corresponding to 0.02% of the administered dose of naringin (111). But a very high dose (500 mg) of the pure com￾pound was administered in this study, and some metabolic pro￾cesses may have been saturated by this nonnutritional intake. Anthocyanins constitute an exception, because intact glycosides are the major circulating forms. The explanation for this may lie in the instability of these molecules in the aglycone form or in a specific mechanism of absorption or metabolism for anthocya￾nins. Passamonti et al (112) have proposed that glycosides of anthocyanins may be transported by bilitranslocase at the gastric level, bacause they have been shown to be good ligands for this carrier. They could also be directly converted into glucuronides by a UDP glucose dehydrogenase as suggested by Wu et al (113). Proanthocyanidins differ from most other plant polyphenols because of their polymeric nature and high molecular weight. This particular feature should limit their absorption through the gut barrier, and oligomers larger than trimers are unlikely to be absorbed in the small intestine in their native forms. In vitro experiments using single layers of Caco-2 cells as a model of absorption in the small intestine showed that only the dimers and trimers of flavanols are able to cross the intestinal epithelium (114). Procyanidin B2 is very poorly absorbed in rats, whereas procyanidin B3 is not absorbed (115, 116). The possibility that procyanidin oligomers are hydrolyzed to mixtures of flavanol monomers and dimers in acidic conditions was suggested by Spencer et al from in vitro experiments (117). However, purified procyanidin dimer B3, as well as grapeseed proanthocyanidins having a higher degree of polymerization, are not degraded to more readily absorbable monomers in rats (116). The stability of proanthocyanidins was investigated in humans by regular anal￾ysis of gastric juice sampled with a gastric probe after ingestion of a proanthocyanidin-rich cocoa beverage (118). This study confirmed that proanthocyanidins are not degraded in the acidic conditions of the stomach in vivo. A minor absorption of some procyanidin dimers seems possible in humans. The procyanidin dimer B2 was detected in the plasma of volunteers after ingestion of a cocoa beverage; however, the maximal plasma concentra￾tion that was reached 2 h after ingestion was much lower than that reached after a roughly equivalent intake of epicatechin (0.04 compared with 6.0mol/L) (119). Proanthocyanidins, which are among the most abundant dietary polyphenols, are very poorly absorbed and may exert only local activity in the gastrointestinal tract or activity mediated by phenolic acids produced through microbial degradation. Their local action may nevertheless be important because the intestine is particularly exposed to oxidiz￾ing agents and may be affected by inflammation and numerous diseases such as cancer (120). Polyphenol concentrations in the colon can reach several hundred micromoles per liter (83), and together with a few carotenoids, polyphenols constitute the only dietary antioxidants present in the colon, because vitamins C and E are absorbed in the upper segments of the intestine. Despite the scarcity of studies performed on the bioavailability of hydroxycinnamic acids, when ingested in the free form, these compounds are rapidly absorbed from the small intestine and are conjugated and, in particular, glucuronidated in the same way that flavonoids are (54, 121). However these compounds are naturally esterified in plant products, and this impairs their ab￾sorption. Human tissues (intestinal mucosa, liver) and biological fluids (plasma, gastric juice, duodenal fluid) do not possess es￾terases capable of hydrolyzing chlorogenic acid to release caffeic acid (122–124). This has also been observed in rats (125, 126). Only the colonic microflora would be capable of carrying out this hydrolysis, and some of the bacterial strains involved have been identified (127). Consequently, as observed for flavonoid gly￾cosides that must be hydrolyzed by the microflora, the efficiency of absorption of phenolic acids is markedly reduced when they are present in the esterified form rather than in the free form (123, 125, 128). In patients who have undergone colonic ablation, caffeic acid was much better absorbed than was chlorogenic acid: 11% and 0.3% of the ingested doses were excreted in urine, respectively (123). Similarly, when chlorogenic acid was given by gavage to rats, no intact compound was detected in plasma in the following 6 h, and the maximum concentrations of metabo￾lites obtained after administration of caffeic acid in the same conditions were 100-fold those of the metabolites (various glu￾curonidated or sulfated derivatives of caffeic and ferulic acids) obtained after chlorogenic acid administration (125). Surpris￾ingly, the plasma concentrations were maximal only 30 min after gavage, which may seem inconsistent with hydrolysis of chlo￾rogenic acid in the cecum. The same observation was made in a human study. When volunteers ingested coffee containing high amounts of esterified phenolic acids but no free caffeic acid, the peak plasma concentration of caffeic acid was observed only 1 h after ingestion of the coffee (129). In this study, the alkaline hydrolysis of coffee showed that chlorogenic acid represented only 30% of the bound caffeic acid. Thus, a possible explanation is that other forms of caffeic acid present in coffee may have been hydrolyzed in the upper part of the gut. Furthermore, the modes of administration used in both studies, ie, direct stomach intuba￾tion in the rat study and ingestion of coffee alone by fasted volunteers in the second study, might allow a rapid transit to the colon and explain the rapid kinetics of appearance of plasma metabolites. However, these 2 studies raise doubt about the total inability of the tissues to hydrolyze esterified phenolic acids. In addition to being esterified to simple acids, hydroxycin￾namic acids may be bound to polysaccharides in plant cell walls; the main example of this is esterification of ferulic acid to arabi￾noxylans in the outer husks of cereals. Although free ferulic acid is reported to be rapidly and efficiently absorbed (up to 25%) from tomatoes in humans (130), its absorption after ingestion of cereals is expected to be much lower because of this esterifica￾tion. Ferulic acid metabolites recovered in the urine of rats rep￾resent only 3% of the ingested dose when ferulic acid is provided as wheat bran, whereas the metabolites represent 50% of the dose when ferulic acid is provided as a pure compound (131). Another study showed that feruloyl esterases are present throughout the entire gastrointestinal tract, particularly in the intestinal mucosa, and that some of the ester bonds between ferulic acid and poly￾saccharides in cell walls may thus be hydrolyzed in the small intestine (126). However, the role of feruloyl esterases seems to be very limited, and absorption occurs mainly in the colon after hydrolysis by enzymes of bacterial origin. Xylanases degrade the 734 MANACH ET AL by guest on February 15, 2012 www.ajcn.org Downloaded from