Effects of isoflavones on breast tissue and the thyroid hormone system in humans: a comprehensive safety evaluation

Abstract

Isoflavones are secondary plant constituents of certain foods and feeds such as soy, linseeds, and red clover. Furthermore, isoflavone-containing preparations are marketed as food supplements and so-called dietary food for special medical purposes to alleviate health complaints of peri- and postmenopausal women. Based on the bioactivity of isoflavones, especially their hormonal properties, there is an ongoing discussion regarding their potential adverse effects on human health. This review evaluates and summarises the evidence from interventional and observational studies addressing potential unintended effects of isoflavones on the female breast in healthy women as well as in breast cancer patients and on the thyroid hormone system. In addition, evidence from animal and in vitro studies considered relevant in this context was taken into account along with their strengths and limitations. Key factors influencing the biological effects of isoflavones, e.g., bioavailability, plasma and tissue concentrations, metabolism, temporality (pre- vs. postmenopausal women), and duration of isoflavone exposure, were also addressed. Final conclusions on the safety of isoflavones are guided by the aim of precautionary consumer protection.

Keywords: Breast tissue; Human intervention studies; Isoflavones; Observational studies; Safety evaluation; Thyroid hormone system.

Fig. 1

Chemical structures of isoflavones in soy and red clover and their glucose conjugates (left row). The 7-O-ß-d-glucosides of daidzein, genistein, and glycitein are named daidzin, genistin, and glycitin. The arrows in the figure indicate the position of glucose conjugation (SKLM 2009)

Fig. 2

Metabolism of daidzein by intestinal microbiota (SKLM 2009)

Fig. 3

Metabolism of genistein by intestinal microbiota (SKLM 2009)

Fig. 4

Mechanism of action of 17β-estradiol and potential interaction of isoflavones with this cascade (modified from Diel 2002). ER estrogen receptor, SERM selective estrogen receptor modulator

Fig. 5

Synthesis and effects of thyroid hormones and potential targets of isoflavones. TSH thyroid-stimulating hormone (also known as thyrotropin), TPO thyroid peroxidase, NIS sodium/iodide symporter, I⁻ iodide, Tg thyroglobulin, I iodine, T4, 3,3′,5,5′-tetraiodo-l-thyronine (also known as l-thyroxine); T3, 3,3′,5-triiodo-l-thyronine; DIO iodothyronine deiodinases, TBG thyroxine-binding globulin, Alb albumin, TTR transthyretin, TTHT transmembrane thyroid hormone transporters, TR thyroid hormone receptor, UGT UDP-glucuronyltransferase, SULT sulfotransferases, SULF sulfonated thyroid hormones, GLUC glucuronidated thyroid hormones; filled square, key points in thyroid hormone cascade; open square, key points of thyroid hormone cascade that are potentially influenced by isoflavones