Polyphenols do not represent an equivalent replacement of Vit E
In the opinion of the authors of this article, at the present time it is not justified to postulate overall that supplements containing polyphenols represent an equivalent replacement ofVit E. Vitamin E (Vit E) is the major lipophilic antioxidant in the acid organism and serves above all to protect polyunsaturated fatty acids in cell membranes against oxidative damage. If high doses of Vit E (a-tocopheryl acetate) in excess of needs are supplied, this can influence the lipid peroxidation and certain associated quality parameters of meat (pig, poultry). With regard to possible alternatives to Vit E supplementing, interest is focusing increasingly on the use of flavonoid-rich plant extracts (for example tea extracts) or industrial by-products (for example grape marc) in feed for productive livestock
Prof. Dr. Siegfried Wolffram, Miriam Luhring
Dr. Ralf Blank, Institute of Animal Nutrition and Physiology
Christian-Albrechts-University of Kiel
Bioavailability of flavonoids
To summarise it can be said that depending on the chemical structure, the dose applied, the form of application and the species studied, the bioavailability of flavonoids can lie between 10 and 50 percent.
Intestinal absorption
Owing to the polarity of intact glycosides, absorption through passive, trans-cellular diffusion does not play any role. Instead, it is postulated that various enzymes and transporters are involved here. For instance a number of studies describe that quercetinmonoglucosides (for example quercetin-3-0-glucoside) can be absorbed via the Na+ dependent glucose transporters SGLTl into the small intestine epithelium and subsequently be split in intra-cellularfashion by an unspecific, cytosolic rJ.-glucosidase (Fig. 2). Furthermore, participation of the monocarboxylate transporter during absorption of catechins from the small intestine is discussed. In addition to this the lactase/phlorizin hydrolase (LPH), a I!.-galactosidase located in the brush border membrane of the small intestine epithelium appears to be involved in the absorption of flavonoid glucosides in the small intestine. According to this the LPH catalyses the extracellular hydrolysis of the sugar residue in the absorptive surface of the small intestine epithelium. The aglycone released in this way is then absorbed by passi- ' ve diffusion in the small intestine epithelium. Flavonoid aglyca and flavonoid glycosides (for example rhamnosides) that cannot be absorbed in the small intestine can be absorbed partially from the large intestine (Fig. 2). Microbial enzymes playa crucial role for the deglycosylation here. In addition to the release of aglyca, comprehensive microbial degradation of proanthocyanidin, flavanols, flavonols and isoflavones takes place. The ABC transporters such as for example the "multidrug resistance associated protein 2" (MRP2) and the "breast cancerrelated protein 1" (BCRP1) play an important role. These transport mechanisms reduce the bioavailability of flavonoids, as one of their tasks is to facilitate exporting into the gut lumen of flavonoid conjugates formed in the small intestine mucosa and absorbed into the small intestine mucosa (Fig. 3).

Figure 1: Structural features of the flavonoid subclasses.
Metabolisation and tissue distribution
On the basis of the extensive metabolisation of flavonoids in the mammal organism described above, considerable quantities of flavonoids ingested orally are eliminated already through the small intestine mucosa membrane and via the gall so that only a variable proportion makes its way into the systemic circulation. Flavonoid conjugates that return to the intestinal lumen via the gall or through the intestinal mucosa can be partially reabsorbed (enterohepatic circulation). In addition to elimination via the gall, renal elimination is important for some flavonoids. For example 3 to 26 per cent of the doses of flavanones, isoflavones or flavonols are eliminated via the urine.
The tissue distribution of the flavonoids and their metabolites after oral ingestion is of particular interest for the transferability of results from in vitro or cell culture experiments as regards their possible relevance for the in vivo situation. After eleven weeks of oral application of quercetin (50 and 500 mg/kg body weight/day) in rats, by far the highest flavonol concentration was detected in the plasma. The lung, that showed the highest concentration of all the organs examined, contained an approximately six times lower flavonol concentration than the plasma. The lowest concentrations lying well below the concentrations described as effective in vitro were detected in the brain and in the white fatty tissue. In a long-term study (50 mg quercetin/ kg body weight/day for four weeks) with pigs, the highest flavonol concentrations were found in the kidney, colon, jejunum and liver. The lowest concentrations were detected in the M. long. dorsi and in the brain. The latter did not differ from the flavonol concentration determined in the plasma. Consequently, only the organs involved in metabolism or elimination offlavonols show higher flavonol concentrations than the plasma. These results indicate that especially in pigs no notable accumulation of flavonols takes place in the tissue even in the case of relatively long periods of application of quercetin. It should be noted here that by comparison with laboratory rodents and humans, pigs also appear to have a substantially higher capacity regarding the first pass elimination (Phase I and Phase II reactions) of flavonoids (own findings, not published), so that findings for laboratory rodents are only transferable to pigs subjectto substantial limitations.

Figure 2: Mechanisms of the intestinal absorption of the flavonol quercetin
Can flavonoids subst itute Vit E supplements?
Lower meat quality is chiefly connected with the oxidation of lipids and fatty-soluble vitamins (for example Vit E). The use ofVit E (atocopheryl acetate) in quantities well exceeding the physiological demand can influence selected meat quality parameters such as, for example, pH value, meat colour and drip juice losses. In connection with possible alternatives to Vit E supplementing, the use of flavonoid-rich plant extracts (for example tea extracts) or industrial by-products (for example grape marc) in feeding productive livestock is currently a subject of intensive discussion. However, clear distinctions must be made between in vitro and in vivo studies, as in vivo the antioxidative effects of flavonoids are influenced by a variety of factors (for example local concentration, bioavailability, metabolisation). There are only a few results from in vivo studies by contrast with the many in vitro findings on the anti oxidative potential offlavonoids that deal with the interactions betweenflavonoids and Vit E. Due to the fact that most of these examinations were carried out on laboratory rodents and these results are regrettably frequently transferred to other species without any critical exploration, only the most important of these results are outlined below before corresponding studies in productive livestock are considered.
Studies on laboratory rodents

Figure 3: Metabolisation of flavonoid·aglyca (sugar-free) in the small intestine mucous membrane and the liver.
Studies on productive livestock.
In growing pigs administration of a green tea polyphenol extract (GTP; 10 and 100 mg GTP/kg body weight/day) with needs-covering Vit E supply (17 I.E./kg diet) over five weeks did not show any influence on the a TOC concentration in the plasma, liver, lung and back muscles, or on meat quality parameters and the antioxidative status. In a further study on pigs, supplementing with green tea catechins (GTC; 200 mg/kg diet) with needs-covering Vit E supply (45 mg a-tocopheryl acetate/kg diet) during final fattening did not have any effect on the a TOC concentration in the back muscles by comparison with the control group (55 mg a-tocopheryl acetate/ kg diet) either. With reference to the lipid peroxidation, however, after storage ofthe muscle meat for ten days under a modified atmosphere (40 per cent C02: 60 per cent 0 2) lower TBARS formation was found in the GTC group by comparison with the control group. In a study on Iberian pigs the application of a flavonoid or polyphenol-rich extract did not lead to any increase in the aTOC concentration or any reduction of lipid peroxidation in the M. long. dorsi. By contrast with the studies presented so far, in which the animals were supplied with Vit E covering needs or extending beyond the physiological demand, our own studies on growing pigs looked at possible Vit E savi ng effects of the flavonol quercetin (10 mg/kg live weight) with short Vit-E supply and additionally induced dietetic-conditioned oxidative stress (addition of 5 per cent fish oil to the diet). Without the addition offish oil the application of quercetin led to higher aTOC concentrations in the plasma and liver after four weeks. Consequently, a Vit Esaving effect of quercetin can be postulated in the case of short Vit E supply without additional "oxidative stress". The feeding of fish oil led to a further depletion of the plasma Vit E concentration and to a significant increase of the 8-isoprostaglandin F2a (8-iso-PGF2a) concentration, a marker for the in vivo lipid peroxidation. Under these conditions the application of quercetin admittedly had no effect on the plasma Vit E concentration, but it reduced the in vivo lipid peroxidation (reduced plasma concentration of 8-isoPGF2a).
Summary and conclusion
As regards the effects of supplementing rations with products containing polyphenols on meat quality parameters, it can be stated that in most of the studies positive effects are described above all on storage of meat. These can be compared "qualitatively" with the effects achieved by higher Vit E doses. In this connection, however, it must be notedthata "quantitative" comparison of various supplements is not possible, on the one hand due to insufficient characterisation and standardisation of most products with a polyphenol contentas regards their composition and the content of potentially active compounds, and on the other hand due to the lack of data regarding the "dose equivalence" of polyphenols and Vit E. In the opinion of the authors of this article, at the present time plant polyphenols are admittedly interesting "active ingredient candidates" in productive animals, but due to the few relevant studies available it is not justified to postulate overall that supplements containing polyphenols represent an equivalent replacement ofVit E. In this connection it should also be noted that both Vit E and polyphenols bring about many effects in the organism that are not based on their antioxidative action mechanisms and have not yet been sufficiently investigated.