Danger of eating soy
Absorption and Metabolism of Soy Isoflavones—from Food to Dietary Supplements and Adults to Infants
It has been known since 1931 that soybeans contain relatively high concentrations of isoflavones (Walz 1931); genistein glycoside was first isolated from soybeans almost 60 years ago (Walter 1941). An appreciation of the hormonal potency of isoflavones became apparent with the recognition in the mid-1940s that an infertility syndrome in sheep was caused by the ingestion of clover containing high levels of the related isoflavonesformononetin and biochaninA (Bennetts et al. 1946). These two methoxylatedisoflavones were metabolized by intestinal bacteria to equol, a unique mammalian isoflavone that shows much greater affinity for binding to estrogen receptors than do the clover-derived isoflavones. The importance of intestinal bacteria for the absorption and metabolism of isoflavones in animals was thus established. There was little clinical or nutritional interest shown in phytoestrogens until the chance discovery of equol in human urine and the recognition that when soy foods were consumed, the levels of isoflavones in urine and blood far exceeded those of endogenous estrogens (Axelson et al. 1984, Setchell et al. 1984). These observations led to the hypothesis that phytoestrogens would be biologically active at these concentrations, conferring health benefits that could explain the relatively low incidence of hormone-dependent diseases in countries in which soy is a dietary staple (Setchell et al. 1984).
Interest in the health-related effects of soy isoflavones has surged in recent years (Setchell 1998, Setchell and Cassidy 1999). Numerous dietary intervention studies have been performed in areas related to cholesterol lowering and cardiovascular effects, effects on bone, and use as an alternative to conventional hormone replacement for postmenopausal women; these studies have given conflicting results. The targeted intake of isoflavones from soy foods has been derived empirically because there are no guidelines for optimal levels of intake. A daily isoflavone intake ≥50 mg has generally been used in clinical studies, largely on the basis of the early observation that a daily intake of 45 mg causes endocrine modulation of the menstrual cycle of premenopausal women (Cassidy et al. 1994). Few dietary intervention studies have attempted to quantify intake or confirm compliance from blood measurements of isoflavones, and the effect of varying dietary intakes of phytoestrogens is largely unknown. Concerns have been expressed that too much isoflavone in the diet may have negative effects, yet there is a paucity of information on the pharmacokinetics of isoflavones or on how varying dietary intake will influence the circulating levels and bioavailability of these bioactive phytoestrogens.
In a series of randomized crossover studies, we examined the pharmacokinetics of daidzein and genistein in healthy adults fed different amounts and types of soy foods. These studies were designed to address whether all soy isoflavone are equal in terms of their apparent bioavailability. Classical pharmacokinetics have established that the volume of distribution in adults is large, indicating a wide tissue distribution, and that the shape of plasma appearance curve is consistent with compounds that undergo enterohepatic recycling. Peak concentrations are seen generally 4–8 h after dietary intake, and the plasma appearance and disappearance in pre- and postmenopausal women are similar. Most of the daidzein and genistein is excreted within the first 24 h, with the average fractional excretion remaining relatively constant over a wide range of intakes, although there is a high individual variability, ranging from 20 to 50% of the dietary intake. Differences are observed in the elimination half-life for different foods. More rapid elimination is observed for isoflavones in a liquid matrix than in a solid matrix food. The bioavailability as determined from the area under the curve is therefore influenced by the food matrix. We have found a curvilinear relationship between the dietary intake of isoflavones and peak plasma concentration and apparent bioavailability, indicating that absorption of isoflavones from food may be saturable. It may be more difficult to attain supraphysiologic levels of isoflavones from foods than from supplements, which are more closely aligned with pharmacologic agents. These findings are relevant to the safety of phytoestrogens. On the basis of the pharmacokinetics of soy isoflavones, maintenance of high steady-state plasma concentrations will be achieved by a regular intake, particularly if phytoestrogens are ingested throughout the day. This approach may serve to maximize the efficacy of phytoestrogens in clinical studies.