No abstract

The soy isoflavones, daidzein and genistein, and the lignans, matairesinol and secoisolariciresinol, are phytoestrogens metabolized extensively by the intestinal microflora. Considerable important evidence is already available that shows extensive interindividual variation in isoflavone metabolism, and we have investigated the extent of this variation in a crossover study of a soy-containing food low or high in isoflavones (each treatment period lasted for 17 days, and the 2 treatment periods were separated by a 25-day washout period) in 24 healthy subjects [19 women and 5 men, mean age 30 yr, range 19-40, mean body mass index 22.5 +/- 3.5 (SD) kg/m2]. There was a 16-fold variation in total isoflavonoid excretion in urine after the high-isoflavone treatment period. The variation in urinary equol excretion was greatest (664-fold), and subjects fell into two groups: poor equol excretors and good equol excretors (36%). A significant negative correlation was found between the proportion of energy from fat in the habitual diet and urinary equol excretion (r = -0.55; p = 0.012). Good equol excretors consumed less fat as percentage of energy than poor excretors (26 +/- 2.3% compared with 35 +/- 1.6%, p < 0.01) and more carbohydrate as percentage of energy than poor excretors (55 +/- 2.9% compared with 47 +/- 1.7%, p < 0.05). Interindividual variation in the urinary excretion of O-desmethyl-angolensin (O-DMA) was also apparent (76-fold after the high-isoflavone treatment period), but there was no relationship between equol excretion and O-DMA excretion. Enterolactone was the major lignan metabolite in urine and plasma but showed less interindividual variation than equol and O-DMA. It is suggested that the dietary fat intake decreases the capacity of gut microbial flora to synthesize equol.

The production of superoxide and nitric oxide individually has been associated with the development of several diseases but only recently has it been realised that interactions between them may also be important in disease pathology. The central hypothesis which is emerging is that the balance between nitric oxide and superoxide generation is a critical determinant in the aetiology of many human diseases including atherosclerosis, neurodegenerative disease, ischaemia-reperfusion and cancer. These ideas are discussed in this short overview and placed in the context of the current and future status of therapies which could modulate the balance between nitric oxide and superoxide.

Background: Oxidative damage to lipids may be involved in the etiology of atherosclerosis, cardiovascular disease in general, and cancer. The soy isoflavone phytoestrogens, genistein and daidzein, and equol (a daidzein metabolite produced by intestinal microflora) are antioxidants in vitro; equol is a particularly good inhibitor of LDL oxidation and membrane lipid peroxidation. Objective: We sought to investigate the effects of a diet enriched with soy containing isoflavones on in vivo biomarkers of lipid peroxidation and resistance of LDL to oxidation, compared with a diet enriched with soy from which the isoflavones had been extracted. Design: A randomized, crossover design was used to compare diets enriched with soy that was low or high in isoflavones in 24 subjects. Plasma concentrations of an F 2 -isoprostane, 8-epiprostaglandin F 2␣ (8-epi-PGF 2␣ ), a biomarker of in vivo lipid peroxidation, and resistance of LDL to copper-ion-induced oxidation were determined. Results: Plasma concentrations of 8-epi-PGF 2␣ were significantly lower after the high-isoflavone dietary treatment than after the low-isoflavone dietary treatment (326 ± 32 and 405 ± 50 ng/L, respectively; P = 0.028) and the lag time for copperion-induced LDL oxidation was longer (48 ± 2.4 and 44 ± 1.9 min, respectively; P = 0.017). Lag time for oxidation of unfractionated plasma and plasma concentrations of malondialdehyde, LDL ␣-tocopherol, polyunsaturated fatty acids, and isoflavonoids did not differ significantly between dietary treatments. Conclusions: Consumption of soy containing naturally occurring amounts of isoflavone phytoestrogens reduced lipid peroxidation in vivo and increased the resistance of LDL to oxidation. This antioxidant action may be significant with regard to risk of atherosclerosis, cardiovascular disease in general, and cancer. Am J Clin Nutr 2000;72:395-400.

Vitamin D is a membrane antioxidant: thus Vitamin D 3 (cholecalciferol) and its active metabolite 1,25-dihydroxycholecalciferol and also Vitamin D 2 (ergocalciferol) and 7-dehydrocholesterol (pro-Vitamin D3) all inhibited iron-dependent liposomal lipid peroxidation. Cholecalciferol, 1,25-dihydroxycholecalciferol and ergocalciferol were all of similar effectiveness as inhibitors of lipid peroxidation but were less effective than 7-dehydrocholesterol; this was a better inhibitor of lipid peroxidation than cholesterol, though not ergosterol. The structural basis for the antioxidant ability of these Vitamin D compounds is considered in terms of their molecular relationship to cholesterol and ergosterol. Furthermore, the antioxidant ability of Vitamin D is compared to that of the anticancer drug tamoxifen and its 4-hydroxy metabolite (structural mimics of cholesterol) and discussed in relation to the anticancer action of this vitamin.