Review ArticleConsumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: Cause, consequence, or epiphenomenon?
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Dietary antioxidant flavonoids
The amounts of antioxidant flavonoids and polyphenols in plant-based foods of the human diet—in particular vegetables, fruits, tea, and wine—are generally much greater than the amounts of other antioxidants in these foods, such as vitamins C and E and carotenoids [14], [15], [16], [17], [18]. Fruits and fruit juices are among the best sources of polyphenols in the human diet because of their high content in most fruits (Table 1) and the relatively large serving sizes (100–200 g). Apples provide
In vitro antioxidant capacity, bioavailability, and metabolism of flavonoids
Flavonoids are strong antioxidants in vitro, mainly due to their low redox potential and their capacity to donate several electrons or hydrogen atoms [30], [31]. For example, catechins have a redox potential of +0.53–0.57 V [31], which from a thermodynamic standpoint enables them to protect urate (+0.59 V), but not ascorbate (+0.28 V), from oxidation by peroxyl radicals (+1.06 V). Quercetin and (−)-epigallocatechin gallate (EGCG) have even lower redox potentials (+0.33 and 0.43 V, respectively
Ex vivo antioxidant protection of human plasma and LDL after consumption of flavonoid-rich foods
When added in vitro to human plasma or isolated LDL, flavonoids can prevent the oxidation of endogenous antioxidants, lipids, and proteins. For example, addition of catechins to plasma protects α-tocopherol, β-carotene, and lipids from oxidation by aqueous peroxyl radicals [76], [77]. Similarly, black tea extract added to plasma strongly inhibits peroxyl radical-induced lipid peroxidation [78]. Theaflavins in black tea, which are formed from partially oxidized catechins, and catechins in green
Total antioxidant capacity of human plasma after consumption of flavonoid-rich foods
Several methods have been used to evaluate the antioxidant capacity of flavonoids and extracts of flavonoid-rich foods and that of human plasma before and after consumption of flavonoid-rich foods. These methods include the ferric-reducing antioxidant potential (FRAP) [104]; oxygen radical absorbance capacity (ORAC), without or with prior precipitation of plasma proteins with perchloric acid (ORAC-PCA) [105]; trolox equivalent antioxidant capacity (TEAC) [106]; and total radical-trapping
Factors affecting the total antioxidant capacity of plasma in humans
Studies assessing the total antioxidant capacity of plasma, serum, or other biological samples often do not take into account possible postprandial or diurnal variations that are not directly related to the intake of dietary antioxidants. Plasma antioxidant capacity may be significantly affected by non-antioxidant dietary constituents that affect uptake, tissue mobilization, or metabolism of endogenous or exogenous antioxidants. Food intake per se may cause variations in the plasma
Increase in plasma urate after consumption of flavonoid-rich foods
As discussed above, the consumption of flavonoid-rich foods is almost always associated with substantial increases in plasma or serum total antioxidant capacity (Table 4). Even when the kinetics of the appearance of flavonoids in plasma and the increase in plasma antioxidant capacity are closely related, the extent of the increase in plasma antioxidant capacity usually far exceeds the plasma concentrations of flavonoids and their metabolites, which are in the nanomolar to low micromolar range (
Antioxidant effects of apples in vitro and in vivo
Apples are one of the main sources of flavonoids in the Western diet [22], [138], [139] and contain as much as 2 g of total phenols per kilogram wet weight, or about 400 mg per apple [15]. The main classes of polyphenols in apples are flavonoids, including quercetin, (−)-epicatechin, (+)-catechin, procyanidins, and anthocyanidins (Fig. 1); dihydrochalcones such as phloretin and phloridzin; and other phenolic compounds such as chlorogenic acid. In an in vitro study, we examined the antioxidant
Fructose-mediated urate production
The rapid and large increases in both plasma urate and antioxidant capacity after apple consumption suggested that the active component(s) is present in apples in relatively large amounts and is easily absorbed. However, apples do not contain urate or its dietary precursors, inosine or other purines. On the other hand, fructose has been known for more than 30 years to increase plasma urate levels consequent to its rapid metabolism by fructokinase [140], [141], [142]. Fructose metabolism in this
Other potential sources of endogenous urate or its derivatives: sucrose, sorbitol, lactate, and methylxanthines
Other carbohydrates in fruit also could influence urate production and plasma antioxidant capacity. Sucrose, which like fructose is present in high amounts in fruits, can undergo hydrolysis in vivo to yield equal amounts of fructose and glucose before absorption. Sucrose can range from 2.5 to 5.0 g per 100 g of apple [144]. In contrast to fructose, glucose does not have a direct effect on plasma urate [143], but may facilitate the absorption of fructose [145]. Solyst et al. [146] demonstrated
Conclusions
Some of the health benefits of fruits and vegetables have been attributed to their content of polyphenols and flavonoids. However, the specific mechanism(s) by which these compounds affect human health remains unclear, despite extensive research conducted in this area in recent years. Most of that research has focused on the antioxidant properties of flavonoids, which are well characterized and well established in vitro. However, the in vitro data often conflict with results obtained from in
Acknowledgments
The work in the authors' laboratory is supported by a grant from the Washington Tree Fruit Research Commission (Wenatchee, WA, USA), NIH Grants P01 AT002034 and T32 AT002688 from the National Center for Complementary and Alternative Medicine, and American Heart Association Grant 03254862. The authors are indebted to Stephen Lawson from the Linus Pauling Institute, Oregon State University, for carefully editing the manuscript.
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