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 have 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. Differences are observed in the elimination half-life for different foods.
More rapid elimination is observed for isoflavones in a liquid matrix than 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 the apparent bioavailability, indicating that absorption of isoflavones from food may be saturable. It may be more difficult to attain supraphysiological levels of isoflavones from foods than from supplements, which are more closely aligned with pharmacological 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 and particularly if phytoestrogens are ingested throughout the day.