Synergistic inhibition of LDL oxidation by phytoestrogens and ascorbic acid

Increasing evidence indicates that oxidative modification of low-density li poprotein (LDL) is an important determinant in atherogenesis, and following menopause, the incidence of coronary heart disease is as prevalent in wome n as it is in men. Estrogen has been demonstrated to inhibit the susceptibi lity of LDL to be oxidized, and more recently the use of phytoestrogens has been considered for estrogen replacement therapy. In this study the antiox idant activity of the three major phytoestrogens: genistein, daidzein, and equol were measured in terms of LDL oxidative susceptibility. Increasing le vels of genistein, daidzein, and equol inhibited LDL oxidation, and this in hibitory effect was further enhanced in the presence of ascorbic acid. The synergism exhibited by these compounds is of clinical importance to phytoes trogen therapy since the efficacy of phytoestrogens as effective antioxidan ts is evident at concentration well within the range found in the plasma of subjects consuming soy products. However, this synergism, combined with th e low reactivity of the phytoestrogens with peroxyl radicals, suggests that an antioxidant mechanism other then free radical scavenging reactions acco unt for the phytoestrogen antioxidant effect, A structural basis for inhibi tion of LDL oxidation involving interaction of the phytoestrogens with apoB -100 is postulated. (C) 2000 Elsevier Science Inc.