Equol

In attempts to prevent a sheep disease, Australian workers wanted (38), a carbocyclic analogue of the natural product equol. ... 

AXELSON M, KIRK D N, FARRANT R D, COOLEY G, LAWSON A M and SETCHELL K D R (1982) The identification of the weak oestrogen equol (17-hydroxy-3-[4-hydroxyphenyl]chroman) in human urine , Biochem J, 210, 353-7. 

DUNCAN M, MERZ-DEMLOW E, XU X, PHIPPS w R and KURZER M s (2000) Premenopausal equol excretors show plasma hormone profiles associated with lowered risk of breast cancer. Cancer Epidemiol Biomarkers Prev 9, 581-6. 

ROWLAND I R, WISEMAN H, SANDERS T A, ADLERCREUTZ H and BOWEY E A (2000) luteriudividual variation in metabolism of soy isoflavones and lignans influence of habitual diet on equol production by the gut microflora. Nutr Cancer 36, 27-32. 

SETCHELL K D R, BROWN N M, LYDEKING-OLSEN E (2002) The cluucal importance of the metabolite equol - a clue to the effectiveness of soy and its isoflavones. JNutr 132, 3577-3584. 

DMA) and equol, while for lignans enterodiol and enterolactone should be used. 

Data on safety have been obtained from in vitro as well as in vivo animal and human studies (see also Section 10.4). About 50 years ago, Australian farmers observed an infertility syndrome in sheep associated with the consumption of clover species (Bennets et al., 1946). The clover compounds shown to cause the infertility (genistein, daidzein, equol, biochanin A, formononetin) were members of the isoflavone family (Bradbury and White, 1951 Shutt and Braden, 1968), raising the question of whether soy might cause infertility in humans (see also Section 10.4.9). A variety of reports further supported adverse effects of isoflavones on animal reproductive systems (Santell et al., 1997 Flynn et al., 2000a,b). 

SHUT D A and braden a w h (1968) The significance of equol in relation to the oestrogenic responses in sheep ingesting clover with a high formononetin content. Austr JAgric Res. 19 545-53. 

Wang X-Y, H-G Hur, JH Lee, KT Kim, S-I Kim (2005) Enantioselective synthesis of 5-equol from dihydro-daidzein by a newly isolated anaerobic human intestinal bacterium. Appl Environ Microbiol 71 214-219. 

Vergne S, Titier K, Bernard V, Asselineau J, Durand M, Lamothe V, Potier M, Perez P, Demotes-Mainard J, Chantre P, Moore N, Bennetau-Pelissero C and Sauvant P. 2007. Bioavailability and urinary excretion of isoflavones in humans effects of soy-based supplements formulation and equol production. J Pharm Biomed Anal 43(4) 1488-1494. 

Fig. 2.86. Chemical structures of the iosflavones daidzein, genistein, O-desmethylangolensin, equol, and the lignans enterolactone and enterodiol. Reprinted with permission from Z. Kuklenyik el al. [209].

C. Atkinson, H.E. Skor, E.D. Fitzgibbons, D. Scholes, C. Chen, K. Wahala, S.M. Schwartz and J.W. Lampe, Urinary equol excretion in relation to 2-hydroxyestrone and 16 alpha-hydroxye-strone concentrations an observational study of young to middle-aged women.. /. Steroid Biochem. Mol. Biol. 86 (2003) 71-77. 

Equol [7-hydroxy-3-(4 -hydroxyphenyl)-chroman] is a nonsteroidal estrogen of the isoflavone class. It is exclusively a product of intestinal bacterial... 

Gut microflora metabolites may also be important. As discussed above, the mammalian lignan aglycones, enterodiol and enterolactone, are estrogenic, and equol is more estrogenic than its dietary precursor, the isoflavone daidzein. ... 

The metabolism and bioavailability of isoflavonoids is likely to be of crucial importance to their ability to help protect human health against disease. Many studies have been published on the metabolism and bioavailability of isoflavones in adults. The metabolism of isoflavones is of particular interest because the potency of isoflavone metabolites differs from that of the parent compounds. The daidzein metabolite equol is three times as potent as is daidzein in an endometrial tumor line. Equol is also a more potent antioxidant in vitro (see Sections 7.3.5 and 7.4.2) ° and the clinical significance of the ability to form equol has been considered in depth. ... 

The importance of the gut microflora in the metabolism of isoflavones has been demonstrated. Antibiotic administration blocks isoflavone metabolism and germfree animals do not excrete metabolites. Moreover, only germfree rats colonized with microflora from a good equol producer excrete equol when fed soy. ... 

Interindividual variation in ability to metabolize daidzein to equol (more estrogenic and a more potent antioxidant than daidzein) could thus influence the potential health protective effects of soy isoflavones. The extent of gut microflora metabolism in humans is variable, approximately 35% of a Western population can produce equol. ... 

A variable metabolic response to isoflavones has been shown for subjects following consumption of soy flour urinary excretion concentrations of genistein, daidzein, equol, and O-DMA were increased 8-, 4-, 45-, and 66-fold, respectively, compared to baseline. Considerable interindividual variation in metabolic response was reported with the peak levels of equol showing the most variation. ... 

Dietary modification, such as feeding wheat bran or soy protein, has been unsuccessful at changing equol-producing capabilitywhich indicates that the intestinal microflora of an individual is relatively stable and resistant to change. 

The possible protective effect of isoflavonoids against prostate cancer has recently been reviewed and it is of particular interest that equol may be a novel antiandrogen that inhibits prostate growth and hormone feedback in rat studies. The role of isoflavonoids in the prevention of breast cancer is, however, the main focus of the next section of this chapter. 

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