Abstract
Dietary phytoestrogens are bioactive compounds with estrogenic activity. With the growing popularity of plant-based diets, the intake of phytoestrogen-rich legumes (especially soy) and legume-derived foods has increased. Evidence from preclinical studies suggests these compounds may have an effect on hormones and health, although the results of human trials are unclear. The effects of dietary phytoestrogens depend on the exposure (phytoestrogen type, matrix, concentration, and bioavailability), ethnicity, hormone levels (related to age, sex, and physiological condition), and health status of the consumer. In this review, we have summarized the results of human studies on dietary phytoestrogens with the aim of assessing the possible hormone-dependent outcomes and health effects of their consumption throughout a lifespan, focusing on pregnancy, childhood, adulthood, and the premenopausal and postmenopausal stages. In pregnant women, an improvement of insulin metabolism has been reported in only one study. Sex hormone alterations have been found in the late stages of childhood, and goitrogenic effects in children with hypothyroidism. In premenopausal and postmenopausal women, the reported impacts on hormones are inconsistent, although beneficial goitrogenic effects and improved glycemic control and cardiovascular risk markers have been described in postmenopausal individuals. In adult men, different authors report goitrogenic effects and a reduction of insulin in non-alcoholic fatty liver patients. Further carefully designed studies are warranted to better elucidate the impact of phytoestrogen consumption on the endocrine system at different life stages.
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Key Points
Phytoestrogens are polyphenolic molecules with a structural similarity to endogenous human hormones, hence their estrogenic activity. The main dietary source of these plant secondary metabolites is legumes (particularly soy), and to a lesser extent fruits, vegetables, and cereals. According to their origin, lignins are classified into plant lignans (e.g., pinoresinol, secoisolariciresinol, matairesinol, and sesamin) and enterolignans (e.g., enterodiol and enterolactone), which are metabolized from plant lignans by intestinal bacteria.
Results from human studies suggest that phytoestrogens may lower the risk of osteoporosis, some cardiometabolic diseases, cognitive dysfunction, breast and prostate cancer, and menopausal symptoms by modulating the endocrine system.
A plausible mechanism of action for phytoestrogens is estrogen receptor (ER) binding. The effects of isoflavones, which have a five-fold greater affinity for β-ER than α-ER, on the endocrine system may be through modulation of the hypothalamic-pituitary axis. They can also activate serotonergic and insulin-like growth factor (IGF) receptors 1, induce free radical binding and modify tyrosine kinases, cycle adenosine monophosphate (cAMP), phosphatidylinositol-3 kinase (PI3K)/Akt, mitogen-activated protein (MAP) kinases, transcription of nuclear factor-kappa β (NF-Kβ), as well as promote DNA methylation and affect histone and RNA expression. In addition, phytoestrogens can act as intracellular regulators of the cell cycle and apoptosis. Thus, due to their antioxidant, antiproliferative, antimutagenic, and antiangiogenic roles, phytoestrogens can improve health. In addition, some authors observed that estrogen and androgen seem to be involved in breast and prostate cancer regulating proliferative and migratory signaling, such as Src/PI3K. Hormonal therapy response may vary depend on interactions between estrogen or androgen receptors and proteins, according to hormone levels. This integrative review aims to synthesize the results obtained by human studies and assess the potential hormone-related health effects of dietary phytoestrogens throughout the human lifespan. This review summarized the results of studies on the effects of dietary phytoestrogens on endocrine regulation in humans. Although preclinical studies (in vitro and in animal models) show phytoestrogens to be potentially estrogenic compounds, triggering anti-estrogenic effects in the organism, the results of epidemiological studies are ambiguous.