The increase in human plasma antioxidant capacity after apple consumption is due to the metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids

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Abstract

Regular fruit consumption lowers the risk of cardiovascular diseases and certain cancers, which has been attributed in part to fruit-derived antioxidant flavonoids. However, flavonoids are poorly absorbed by humans, and the increase in plasma antioxidant capacity observed after consumption of flavonoid-rich foods often greatly exceeds the increase in plasma flavonoids. In the present study, six healthy subjects consumed five Red Delicious apples (1037 ± 38 g), plain bagels (263.1 ± 0.9 g) and water matching the carbohydrate content and mass of the apples, and fructose (63.9 ± 2.9 g) in water matching the fructose content and mass of the apples. The antioxidant capacity of plasma was measured before and up to 6 h after food consumption as ferric reducing antioxidant potential (FRAP), without or with ascorbate oxidase treatment (FRAPAO) to estimate the contribution of ascorbate. Baseline plasma FRAP and FRAPAO were 445 ± 35 and 363 ± 35 μM trolox equivalents, respectively. Apple consumption caused an acute, transient increase in both plasma FRAP and FRAPAO, with increases after 1 h of 54.6 ± 8.7 and 61.3 = 17.2 μM trolox equivalents, respectively. This increase in plasma antioxidant capacity was paralleled by a large increase in plasma urate, a metabolic antioxidant, from 271 ± 39 μM at baseline to 367 ± 43 μM after 1 h. In contrast, FRAP and FRAPAO time-dependently decreased after bagel consumption, together with urate. Consumption of fructose mimicked the effects of apples with respect to increased FRAP, FRAPAO, and urate, but not ascorbate. Taken together, our data show that the increase in plasma antioxidant capacity in humans after apple consumption is due mainly to the well-known metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids.

Introduction

Regular consumption of fruits and vegetables lowers the risk of cardiovascular diseases, certain types of cancer, and other chronic diseases [1], [2]. These beneficial effects of fruits and vegetables have been attributed in part to their high content of flavonoids, the intake of which also is inversely associated with the incidence of many chronic diseases [3], [4], [5]. Apples are one of the main sources of flavonoids in the Western diet, together with tea, wine, onions, and chocolate [4], [5], [6]. An increased intake of apples has been correlated with a decreased risk of heart disease and type 2 diabetes [3]. In addition, apple consumption has been associated with a decreased incidence of thrombotic stroke [7].

The mechanism(s) by which flavonoids in fruits and vegetables may lower chronic disease risk remains to be fully elucidated. Most flavonoids have antioxidant properties, and extracts and juices of fruits and vegetables exhibit substantial antioxidant capacity in vitro [8], [9], [10]. Therefore, it is conceivable that the health benefits of flavonoid-rich foods are related to the antioxidant protection of biological macromolecules, such as lipids, proteins, and DNA. However, this notion remains controversial. Although some studies have failed to show a short- or long-term antioxidant effect in humans of consumption of fruits, vegetables, or flavonoids [11], [12], [13], other studies have reported such effects, in particular an acute increase in the antioxidant capacity of plasma [14], [15], [16]. Interestingly, flavonoids are poorly absorbed by humans [17], and the increase in plasma antioxidant capacity observed after consumption of flavonoid-rich foods often greatly exceeds the increase in plasma flavonoids [18], [19], [20].

In addition, we recently found that apple extracts added to human plasma in vitro significantly protected endogenous urate, α-tocopherol, and lipids from free radical-mediated oxidation, but such antioxidant effects were not observed in plasma ex vivo after apple consumption by healthy subjects [21]. These data suggest that apple-derived flavonoids are not absorbed in sufficient amounts to significantly contribute to the antioxidant defenses in plasma in vivo.

In follow-up to these observations [21], we investigated the effects of apple consumption in humans on plasma antioxidant levels and total antioxidant capacity. We found a transient increase in plasma antioxidant capacity after apple consumption, which was explained by a transient increase in plasma urate. Furthermore, we discovered that very similar increases in plasma antioxidant capacity and urate could be achieved by consumption of fructose.

Section snippets

Materials

Ascorbic acid, uric acid, ferric chloride (FeCl3), diethylenetriaminepentaacetic acid (DTPA), and ascorbate oxidase were purchased from Sigma (St. Louis, MO, USA). 2,4,6-Tri(2-pyridil)-s-triazine (TPTZ) was purchased from Fluka (Milwaukee, WI, USA). Chelex Resin 100 was purchased from Bio-Rad (Hercules, CA, USA). Water used in experiments was deionized (Milli Q) and additionally treated overnight with Chelex and then filtered. All solvents used were of high-performance liquid chromatography

Effect of apple consumption on plasma FRAP and antioxidants in humans

Plasma was obtained from six healthy subjects before and up to 6 h after consumption of five apples, and FRAP, ascorbate, and urate were determined. Plasma FRAP was 445 ± 35 μM trolox equivalents (TE) at baseline. After apple consumption, FRAP increased significantly (p < .0001, repeated-measures ANOVA), with a 12% increase (54.6 ± 8.7 μM TE) after 1 h (Fig. 1A). To assess the contribution of ascorbate, FRAP was analyzed after incubation of plasma with ascorbate oxidase. Baseline FRAPAO (363 ±

Discussion

In this in vivo study, we investigated the short-term effect of consuming five Red Delicious apples on plasma antioxidant capacity in six healthy subjects. One hour after apple consumption, a large, statistically significant increase in plasma antioxidant capacity was observed, as assessed by FRAP. This increase in FRAP could have been due to the absorption and uptake into the circulation of antioxidant flavonoids from apples. However, our subsequent analyses showed that the antioxidant

Acknowledgements

This work was supported by a grant from the Washington Tree Fruit Research Commission (Wenatchee, WA, USA). The authors thank Leslee Lucas and her staff (Student Health Services, Oregon State University, Corvallis, OR, USA) for their assistance in drawing blood, and the volunteers of the Linus Pauling Institute who participated in this study.

References (41)

  • R.A Caccetta et al.

    Ingestion of red wine significantly increases plasma phenolic acid concentrations but does not acutely affect ex vivo lipoprotein oxidizability

    Am. J. Clin. Nutr.

    (2000)
  • B Kirschbaum

    Renal regulation of plasma total antioxidant capacity

    Med. Hypoth.

    (2001)
  • M.H Alderman

    Uric acid and cardiovascular risk

    Curr. Opin. Pharmacol.

    (2002)
  • K.J Joshipura et al.

    The effect of fruit and vegetable intake on risk for coronary heart disease

    Ann. Intern. Med.

    (2001)
  • P Knekt et al.

    Flavonoid intake and coronary mortality in Finland: a cohort study

    Br. Med. J.

    (1996)
  • M.G Hertog et al.

    Flavonoid intake and long-term risk of coronary heart disease and cancer in the Seven Countries Study

    Arch. Intern. Med.

    (1995)
  • I.C Arts et al.

    Catechin intake and associated dietary and lifestyle factors in a representative sample of Dutch men and women

    Eur. J. Clin. Nutr.

    (2001)
  • P Knekt et al.

    Quercetin intake and the incidence of cerebrovascular disease

    Eur. J. Clin. Nutr.

    (2000)
  • J.A Vinson et al.

    Phenol antioxidant quantity and quality in foods: fruits

    J. Agric. Food Chem.

    (2001)
  • A.R Proteggente et al.

    The antioxidant activity of regularly consumed fruit and vegetables reflects their phenolic and vitamin C composition

    Free Radic. Res.

    (2002)
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