Fruit Hydroxycinnamic Acids Inhibit Human Low-Density Lipoprotein Oxidation in Vitro Anne S. Meyer,* ,† Jennifer L. Donovan, ‡ Debra A. Pearson, † Andrew L. Waterhouse, ‡ and Edwin N. Frankel † Department of Food Science and Technology and Department of Viticulture and Enology, University of California, Davis, California 95616 Oxidative modification of low-density lipoprotein (LDL) is believed to play a crucial role in atherogenesis. The antioxidant activity of hydroxycinnamic acids typically present in fruits was investigated in vitro using a human LDL oxidation assay. The o-dihydroxy compounds caffeic, caftaric, chlorogenic, and neochlorogenic acids had highest antioxidant activities and inhibited LDL oxidation from 86 to 97% at 5 µM. Ferulic and fertaric acids had lower antioxidant activities, and p-coumaric and p-coutaric acids had the lowest. Differences in antioxidant activity were thus primarily related to the hydroxylation and methylation pattern. The esterification to tartaric acid slightly enhanced the antioxidant activity of p-coumaric and ferulic acids, but esterification of caffeic acid to quinic acid (as in chlorogenic and neochlorogenic acid) had no effect on or slightly decreased antioxidant activity. The observed differences in activities are discussed in terms of structural dissimilarities of the compounds. It is proposed that for the less active hydroxycinnamic acids, p-coumaric and ferulic acids, esterification to tartaric acid may enhance their ability to inhibit LDL oxidation by binding to apolipoprotein B in the LDL particle. Keywords: Antioxidant; LDL; p-coumaric, ferulic, caffeic, hydroxycinnamoyltartaric acids; hy- droxycinnamoylquinic acids INTRODUCTION Oxidative modification of low-density lipoprotein (LDL) is believed to be implicated in atherogenic plaque formation, which is one of the main causes of coronary heart disease (Steinberg, 1988). Dietary antioxidants that protect LDL from oxidation may therefore reduce atherogenesis and prevent coronary heart disease (Es- terbauer et al.,1992; Frankel et al., 1993; Kinsella et al., 1993). There is strong evidence from epidemiological data that consumption of fresh fruits is associated with a lowered risk of coronary heart disease mortality (Criqui and Ringel, 1994). This apparent cardioprotec- tive action of fruits is currently believed to be at least partly attributable to the antioxidant activity of ascorbic acid, -carotene, tocopherols, and flavonoids abundant in fruits and other plant foods (Gey, 1995; Hertog et al., 1993, 1995; Kinsella et al., 1993). Comparatively little is known about the antioxidant and potential biological activities of hydroxycinnamic acid compounds. Hy- droxycinnamic acids are phenolic compounds ubiqui- tously present in plant foods. Their chemical structures consist of a phenolic ring with a lateral three-carbon chain (C 6 -C 3 ) (Figure 1) (Macheix et al., 1990). In the diet, hydroxycinnamic acids are largely derived from fruits, grains, and coffee. In fruits, hydroxycin- namic acids are mainly derived from p-coumaric, caffeic, and ferulic acids and predominantly occur in esterified form with quinic acid or glucose (Herrmann, 1989). Hydroxycinnamoylquinic acids are the quantitatively most dominant form in pome and stone fruits, with chlorogenic acid (5′-caffeoylquinic acid) being predomi- nant in apples, pears, and peaches and neochlorogenic * Address correspondence to this author at the Department of Biotechnology, Technical University of Denmark, DK-2800 Lyngby, Denmark [fax (+45) 45 88 49 22; e-mail am@ibt.dtu.dk]. † Department of Food Science and Technology. ‡ Department of Viticulture and Enology. Figure 1. Structures of the hydroxycinnamic acids and their derivatives used in this study. 1783 J. Agric. Food Chem. 1998, 46, 1783-1787 S0021-8561(97)00896-0 CCC: $15.00 © 1998 American Chemical Society Published on Web 04/25/1998