Plasma Enterolignans Are Associated with Lower Colorectal Adenoma Risk

Abstract

Lignans are biphenolic compounds that occur in foods of plant origin such as whole grains, seeds, fruits and vegetables, and beverages, such as coffee and tea. Plant lignans are converted by intestinal bacteria into the enterolignans, enterodiol and enterolactone. Enterolignans possess several biological activities, whereby they may influence carcinogenesis. We studied the associations between plasma enterolignans and the risk of colorectal adenomas in a Dutch case-control study. Colorectal adenomas are considered to be precursors of colorectal cancer. Cases (n = 532) with at least one histologically confirmed colorectal adenoma and controls (n = 503) with no history of any type of adenoma were included. Plasma enterodiol and enterolactone concentrations were measured by liquid chromatography with tandem mass spectrometry. Associations were stronger for incident than for prevalent cases. When only incident cases (n = 262) were included, high compared to low plasma concentrations of enterodiol were associated with a reduction in colorectal adenoma risk after adjustment for confounding variables. Enterodiol odds ratios (95% confidence intervals) were 1.00, 0.69 (0.42-1.13), 0.60 (0.37-0.99), and 0.53 (0.32-0.88) with a significant trend (P = 0.01) through the quartiles. Although enterolactone plasma concentrations were 10-fold higher, enterolactone's reduction in risk was not statistically significant (P for trend = 0.09). Use of oral antibiotic therapy could decrease the plasma concentrations of enterolactone. Exclusion of antibiotic users resulted in similar odds ratios for both enterolignans, but the association for enterolactone became somewhat stronger (P = 0.05 versus P = 0.09). We observed a substantial reduction in colorectal adenoma risk among subjects with high plasma concentrations of enterolignans, in particular, enterodiol. These findings could be important in the prevention of colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1132 -6)

Lack of Prospective Associations between Plasma and Urinary Phytoestrogens and Risk of Prostate or Colorectal Cancer in the European Prospective into Cancer-Norfolk Study

“…To our knowledge, this is the only other study of colorectal cancer and phytoestrogen biomarkers that has been published; its overall conclusion is congruent with the results of the present study. A retrospective study reported a decreased likelihood of colorectal adenomas, the precursors to colorectal cancer, among those with higher serum enterodiol levels, and a near-significant trend of decreasing OR values across enterolactone quartiles upon exclusion of antibiotic users (P = 0.05), but is not appropriate for comparison with the present results due to substantial differences in study design and end points (30). The strengths of the present study include the breadth of data available for controlling potential confounders, and its prospective design, thus avoiding bias among cases for their biomarker samples and questionnaire on dietary and questions on health behavior.…”

Role of ABCG2 in Transport of the Mammalian Lignan Enterolactone and its Secretion into Milk in Abcg2 Knockout Mice

“…A significant concentration of enterolactone has been reported in bovine milk (Antignac et al, 2004). In general, under normal dietary conditions, enterolactone is the enterolignan that reaches the highest concentration in plasma (Kuijsten et al, 2006;Högger, 2013) and is the most effective metabolite in the inhibition of cell proliferation (Corsini et al, 2010;Azrad et al, 2013). Owing to the potential beneficial effects of enterolactone and the complex relationship between the colonic environment and other factors contributing to systemic exposure of such compounds to ABC transporters, a study of the interaction of ABCG2 with enterolactone could be of particular relevance.…”

The Comparison of Rat and Human Intestinal and Hepatic Glucuronidation of Enterolactone Derived from Flaxseed Lignans

“…A growing body of evidence suggests that SDG and its metabolites, in particular EL, may exert protective effects against cancers such as prostate, breast and colon cancer 22,31,43,44 , CVD 26,28 , inflammation 45 , and oxidative damage through diverse mechanisms including phytoestrogenic 46 and antioxidant effects 47 from both in vitro and in vivo studies. Epidemiological studies also suggest that the lower risk of the aforementioned chronic diseases is greatly attributed to high circulating concentrations of EL [48][49][50][51] . Hence, as the promising bioactive form of lignan, the health benefits, mechanisms of the biological effects as well as the pharmacokinetic properties of EL will be discussed below.…”