The oxidation of low density lipoproteins (LDLs) is thought to take place in the arterial intima when the particles have become isolated from circulating water-soluble antioxidants. We hypothesized that isoflavonoid antioxidants derived from soy could be incorporated into lipoproteins and possibly could protect them against oxidation, which is regarded as atherogenic. Six healthy volunteers received 3 soy bars [containing the isoflavonoid antioxidants genistein (12 mg) and daidzein (7 mg)] daily for 2 weeks. LDLs were isolated from blood drawn at the the end of a 2-week dietary baseline period, after 2 weeks on soy, and after discontinuation of soy. Large increases in plasma isoflavonoid levels occurred during soy feeding, but only minute amounts were stably associated with lipoproteins (less than 1% of plasma isoflavonoids in the LDL fraction). The LDLs were subjected to copper-mediated oxidation in vitro . Compared with off soy values, lag phases of LDL oxidation curves were prolonged by a mean of 20 min ( P < 0.02) during soy intake, indicating a reduced susceptibility to oxidation. The results suggest that intake of soy-derived antioxidants, such as genistein and daidzein, may provide protection against oxidative modification of LDL. As only very small amounts of these substances were detected in purified LDL, modified LDL particles may have been produced in vivo by circulating isoflavonoids promoting resistance to oxidation ex vivo .

Because many Western diseases are hormone-dependent cancers, we have postulated that the Western diet, compared with a vegetarian or semi-vegetarian diet, may alter hormone production, metabolism or action at the cellular level. Recently, our interest has been focused on the cancer-protective role of some hormone-like diphenolic phytoestrogens of dietary origin, the lignans and isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids but also lignans), as well as whole grain cereals, seeds, probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds with weak estrogenic and antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation and angiogenesis, making them strong candidates for a role as natural cancer protective compounds. Epidemiological investigations support this hypothesis, because the highest levels of these compounds are found in countries or regions with low cancer incidence. This report is a review of results that suggest that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds.

Interindividual differences in metabolism of the soy isoflavone, daidzein, to equol and O-desmethylangolensin (ODMA) by human gut bacteria, have been associated with altered risk of cancer and other chronic diseases, according to some studies. Differences have been reported in the prevalence of the equol-producer phenotype among populations, with a higher prevalence in soy-consuming Asian populations than in Western populations. To date, prevalence of the daidzein-metabolizing phenotypes in Asians, compared with Caucasians, has not been evaluated in the context of a standardized phenotyping method. We assessed the prevalence of equol- and ODMA-producer phenotypes in 91 Korean American (KA) women and girls living in the Seattle, Washington area and compared this with previous similarly collected prevalence data in Caucasian American (CA) women and girls (n = 222). We also compared the dietary habits of the 2 groups. Isoflavonoid concentrations in first-void morning urines, collected after a 3-d soy challenge, were used to establish equol-, and ODMA-producer phenotypes (>44 μg/L). The prevalence of the equol-producer phenotype was higher (51 vs. 36%; P = 0.015) and the ODMA-producer phenotype was lower (84 vs. 92%, P = 0.03) in KA than in CA women and girls. KAs consumed approximately 3 times more soy foods than the CAs, but no significant associations were found between the consumption of soy foods and equol-producer phenotype. Our findings support the reports that, compared with Western populations, Asian populations have a higher equol-producer prevalence. The additional observation that the prevalence of the ODMA-producer phenotype is lower in KAs suggests that daidzein-metabolizing patterns in general may differ between KAs and CAs.

Background/objectives: Studies have observed associations between the gut microbiome and obesity. O-desmethylangolensin (ODMA) and equol are gut bacterial metabolites of daidzein, a compound found in high amounts in soy foods. Approximately 80–95% and 25–60% of individuals harbor gut microbial communities capable of producing ODMA or equol, respectively. Given that other phenotypes of gut bacterial metabolism of dietary compounds have been associated with obesity, we hypothesized that daidzein-metabolizing phenotypes would be associated with obesity. The objective of this study was to compare the prevalence of ODMA-producer and equol-producer phenotypes in obese, overweight and normal-weight individuals. Subjects/methods: Adults aged 18–95 years (n=297) provided a first-void urine sample after a 3-day soy challenge, and urinary ODMA and equol concentrations were used to classify individuals as producers or non-producers. Body mass index was calculated from self-reported weight and height. Results: There were 60 ODMA non-producers and 173 equol non-producers. Obese individuals were 2.8 times more likely to be ODMA non-producers (odds ratio (OR)=2.8, 95% confidence interval (CI): 1.2, 6.2) compared with normal-weight individuals, when adjusted for age, race (white vs non-white), and gender and menopausal status (male, premenopausal female and postmenopausal female). Obesity was not associated with equol-producer phenotype (OR=1.1, 95% CI: 0.5, 2.2). Stronger associations with obesity were observed in the ODMA non-producers who were also equol producers than in the equol non-producers. Conclusions: Results from this analysis suggest that the ODMA-producer phenotype, but not equol-producer phenotype, is associated with obesity in adults. These results support further work to replicate these findings and evaluate the mechanisms of the observed associations.