Phytoestrogens: Dietary Intake, Bioavailability, and Protective Mechanisms against Colorectal Neoproliferative Lesions

Abstract

Phytoestrogens are natural substances that have been extensively studied for their beneficial effect on human health. Herein, we analyzed the data of the literature on the role of phytoestrogens in the prevention of colorectal neoproliferative lesions (CNL). Both in vitro and in vivo studies suggest that the beneficial effects of phytoestrogens on CNL mainly depend on their ability to bind estrogen receptor beta (ERβ) in the intestinal mucosa and counter ER-alpha (ERα) activity. Epidemiological data demonstrate a correlation between the low prevalence of CNL in Eastern populations and the consumption of soy products (phytoestrogen-enriched diet). However, both observational and interventional studies have produced inconclusive results. In our opinion, these discrepancies depend on an inadequate evaluation of phytoestrogen intake (dietary questionnaires were not aimed at establishing phytoestrogen intake) and absorption (depending mainly on the intestinal microbiota of the analyzed subjects). For this reason, in the present review, we performed an overview of phytoestrogen dietary intake and metabolism to offer the reader the opportunity for a better interpretation of the literature. Future prospective trials focusing on the protective effect of phytoestrogens against CNL should take into account both their dietary intake and absorption, considering the effective role of the intestinal microbiota.

Keywords: colon adenomas; colorectal cancer; estrogen receptors; familial adenomatous polyposis; intestinal microbiota.

Figure 1

Absorption, metabolism, and excretion of phytoestrogens. Daidzin, contained in soy products, is hydrolyzed by the bacterial beta-glucosidase generating aglycones (primary metabolites). In addition, the colonic microflora is capable of transforming aglycones into secondary metabolites and bacterial end-products that are eliminated with feces. Both primary and secondary metabolites undergo either glucuronidation or sulfidation by intestinal epithelial cells and hepatocytes. Once in the bloodstream, these conjugated products reach target tissues and later on are excreted in urine or bile. In the latter case, they can be absorbed again by the intestine (enterohepatic circulation) or are excreted in feces as bacterial end-products or unconjugated forms.