Interactions between soy isoflavones and other bioactive compounds: a review of their potentially beneficial health effects

Isoflavones are phytoestrogens with potent estrogenic activity; genistein, daidzein and glycitein are the most active isoflavones found in soy beans. Phytoestrogens have similarity in structure with the human female hormone 17-β-estradiol, which can bind to both alpha and beta estrogen receptors, and mimic the action of estrogens on target organs, thereby exerting many health benefits when used in some hormone-dependent diseases. Numerous clinical studies claim benefits of genistein and daidzein in chemoprevention of breast and prostate cancer, cardiovascular disease and osteoporosis as well as in relieving postmenopausal symptoms. The ability of isoflavones to prevent cancer and other chronic diseases largely depends on pharmacokinetic properties of these compounds, in particular absorption and distribution to the target tissue. The chemical form in which isoflavones occur is important because it influences their bioavailability and, therefore, their biological activity. Glucose-conjugated isoflavones are highly polar, water-soluble compounds. They are hardly absorbed by the intestinal epithelium and have weaker biological activities than the corresponding aglycone. Different microbial families of colon can transform glycosylated isoflavones into aglycones. Clinical studies show important differences between the aglycone and conjugated forms of genistein and daidzein. The evaluation of isoflavone metabolism and bioavailability is crucial to understanding their biological effects. Lipid-based formulations such as drug incorporation into oils, emulsions and self-microemulsifying formulations have been introduced to increase bioavailability. Complexation with cyclodextrin also represent a valid method to improve the physicochemical characteristics of these substances in order to be absorbed and distributed to target tissues. We review and discuss pharmacokinetic issues that critically influence the biological activity of isoflavones.

Soy protein and isoflavones (phytoestrogens) have gained considerable attention for their potential role in improving risk factors for cardiovascular disease. This scientific advisory assesses the more recent work published on soy protein and its component isoflavones. In the majority of 22 randomized trials, isolated soy protein with isoflavones, as compared with milk or other proteins, decreased LDL cholesterol concentrations; the average effect was approximately 3%. This reduction is very small relative to the large amount of soy protein tested in these studies, averaging 50 g, about half the usual total daily protein intake. No significant effects on HDL cholesterol, triglycerides, lipoprotein(a), or blood pressure were evident. Among 19 studies of soy isoflavones, the average effect on LDL cholesterol and other lipid risk factors was nil. Soy protein and isoflavones have not been shown to lessen vasomotor symptoms of menopause, and results are mixed with regard to soy's ability to slow postmenopausal bone loss. The efficacy and safety of soy isoflavones for preventing or treating cancer of the breast, endometrium, and prostate are not established; evidence from clinical trials is meager and cautionary with regard to a possible adverse effect. For this reason, use of isoflavone supplements in food or pills is not recommended. Thus, earlier research indicating that soy protein has clinically important favorable effects as compared with other proteins has not been confirmed. In contrast, many soy products should be beneficial to cardiovascular and overall health because of their high content of polyunsaturated fats, fiber, vitamins, and minerals and low content of saturated fat.

Convincing evidence shows that soy protein intake has beneficial effects on lipid changes, but it is unclear which components of soy protein are responsible. We conducted a meta-analysis to identify and quantify the effects of soy protein containing isoflavones on the lipid profile. Twenty-three eligible randomized controlled trials published from 1995 to 2002 were identified from the PUBMED database (National Library of Medicine, Bethesda, MD). Weighted mean effect sizes were calculated for net changes in serum lipid concentrations by using fixed-effect or random-effect models. Pre-specified subgroup analyses were performed to explore the influence of covariates on net lipid change. Soy protein with isoflavones intact was associated with significant decreases in serum total cholesterol (by 0.22 mmol/L, or 3.77%), LDL cholesterol (by 0.21 mmol/L, or 5.25%), and triacylglycerols (by 0.10 mmol/L, or 7.27%) and significant increases in serum HDL cholesterol (by 0.04 mmol/L, or 3.03%). The reductions in total and LDL cholesterol were larger in men than in women. Initial total cholesterol concentrations had a powerful effect on changes in total and HDL cholesterol, especially in subjects with hypercholesterolemia. Studies with intakes >80 mg showed better effects on the lipid profile. The strongest lowering effects of soy protein containing isoflavones on total cholesterol, LDL cholesterol, and triacylglycerol occurred within the short initial period of intervention, whereas improvements in HDL cholesterol were only observed in studies of >12 wk duration. Tablets containing extracted soy isoflavones did not have a significant effect on total cholesterol reduction. Soy protein containing isoflavones significantly reduced serum total cholesterol, LDL cholesterol, and triacylglycerol and significantly increased HDL cholesterol, but the changes were related to the level and duration of intake and the sex and initial serum lipid concentrations of the subjects.