Enterolactone metabolism

Recently, some of the specific faecal bacteria involved in the metabolism of dietary isoflavonoids were isolated (Hur et al., 2000). They have been shown to selectively convert genistin and daidzin to their respective aglycones. One of the isolated bacteria, under anoxic conditions, was further shown to metabolise genistein and daidzein to their respective dihydroxy-genistein and dihydroxy-daidzein. In the case of lignans, enterodiol and enterolactone were shown to be excreted in vivo only in rats harbouring a gut microflora (Rowland et al, 1999). 

Substantial individual differences were observed in the response to study breads and the ranges of enterolactone concentration changes in the groups were as follows -54.5-60.0 nmol/1 (placebo), -26.2-101.3 nmol/1 (LP), -19.6-81.8 nmol/1 (HP). This was something that could have been expected as in several studies dietary factors have explained only 10% of the variation in serum enterolactone (Vanharanta et al, 2002b Kilkkinen et al., 2001). This gives further support to the major role of intestinal bacteria in the synthesis of enterolactone. Decreased concentrations of enterolactone may occur due to an increased fiber intake, which may shorten the retention time in the colon and lead to incomplete metabolism of plant lignans. Constipation was earlier shown to be associated with an increased level of serum enterolactone (Kilkkinen et al., 2001). 

Dean, B., Chang, S., Doss, G.A., King, C., and Thomas, P.E., Glucuronidation, oxidative metabolism, and bioactivation of enterolactone in rhesus monkeys. Arch. Biochem. Biophys., 429, 244, 2004. 

Heinonen, S., Nurmi, T., Liukkonen, K., Poutanen, K., Wahala, K., Deyama, T., Nishibe, S., and Adlercreutz, H., In vitro metabolism of plant lignans new precursors of mammalian lignans enterolactone and enterodiol, J. Agric. Food Chem., 49, 3178, 2001. 

Jacobs, E. and Metzler, M. 1999. Oxidative metabolism of the mammalian lignans enterolactone and enterodiol by rat, pig, and human liver microsomes. J. Agric. Food Chem. 47, 1071— 1077. 

FIGURE 17.1 Proposed metabolic pathway of (+)-pinoresinol diglucoside to enterolactone. 

S Heinonen, T Nurmi, K Liukkonen, K Potanen, K Wahala, T Deyama, S Nishibe, Adlercreutz. In Vitro Metabolism of plant bgnans New precursors of mammalian lignans enterolactone and enterodiol. J Agric Food Chem 49 3178-3186, 2001. 

Serum enterolactone was measured in a cross-sectional study in Finnish adults. In men, serum enterolactone concentrations were positively associated with consumption of whole-grain products. Variability in serum enterolactone concentration was great, suggesting the role of gut microflora in the metabolism of hgnans may be important. Kilkkinen et al. also report that intake of lignans is associated with... 

Adlercreutz H, Van der Wildt J, Kinzel J. Lignan and isoflavonoid conjugates in human urine. / Steroid Biochem Mol Biol. 1995 52 97—103. Jansen GHE, Arts ICW, Nielen MWF, Muller M, Hollman PCH, Keijer J. Uptake and metabolism of enterolactone and enterodiol by human colon epithelial cells. Arch Biochem Biophys. 2005 435 74-82. 

Fig. 78.1 (continued) given in brackets (large interindividual differences are observed due to various dietary habits and ability to metabolize polyphenols). Abbreviations ED enterodiol, EL enterolactone, GET gastrointestinal tract, LARI lariciresinol, 0-DMA 0-desmethylangolensin, R residues (—H, —OH, or —CH3), SECO secoisolariciresinol, SDG secoisolariciresinol diglucoside... 

SDG directly lowers serum cholesterol. Because lignans modulate the enzymes 7-hydroxylase and acyl CoA cholesterol transferase, they may be able to decrease serum cholesterol, as both of these enzymes are involved in cholesterol metabolism. Lignans may also lower oxidative stress. Enterodiol, enterolactone, and SDG act as antioxidants by inhibiting the peroxidation of PUFA in vitro at levels that may be achievable in vivo. Inhibiting peroxidation of PUFA may decrease oxidation of low-density lipoprotein, a key player in atherogenesis. Finally, SDG has been reported to act as an antagonist of platelet-activating factor (PAF) [58]. 

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