Equol

Equol
Names
IUPAC name
(3S)-3-(4-Hydroxyphenyl)-7-chromanol
Other names
4',7-Isoflavandiol
Identifiers
531-95-3 YesY
3D model (Jmol) Interactive image
Interactive image
ChEMBL ChEMBL198877 YesY
ChemSpider 82594 YesY
ECHA InfoCard 100.007.749
KEGG C14131 YesY
PubChem 91469
Properties
C15H14O3
Molar mass 242.27 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Equol (4',7-isoflavandiol) is an isoflavandiol[1] metabolized from daidzein, a type of isoflavone, by bacterial flora in the intestines.[2] While endogenous estrogenic hormones such as estradiol are steroids, equol is a non-steroidal estrogen. However, only about 30-50% of people have intestinal bacteria that make equol.[3] Equol can exist in two enantiomeric forms, (S)-equol and (R)-equol.[4] (S)-Equol preferentially binds estrogen receptor beta.[2][5]

History

(S)-Equol was first isolated from horse urine in 1932,[6] and the name was suggested by this equine connection.[7] Since then, equol has been found in the urine or plasma of many other animal species, although these animals have significant differences in their effectiveness in metabolizing the soy isoflavone daidzein into equol.[7] In 1980, scientists reporting the discovery of equol in humans.[8] The ability of (S)-equol to play a role in the treatment of estrogen- or androgen-mediated diseases or disorders was first proposed in 1984.[9]

Chemical structure

Equol is a compound that can exist in two mirror image forms known as the enantiomers, (S)-equol and (R)-equol. However, only (S)-equol is produced in humans and animals with the ability to produce equol after soy isoflavone consumption. (S)-Equol is not of plant origin. It is a metabolite of the soy isoflavone daidzein. (S)-equol thus is characterized as an isoflavan.[7] In contrast, R-equol is not made in humans, but can be chemically synthesized, such as in the laboratory.[10] The molecular and physical structure of (S)-equol is similar to that of the hormone estradiol.[11]

Production in humans

Not all humans can produce (S)-equol after soy consumption.[9] The ability to do so depends on having certain strains of bacteria living within the intestine. Twenty-one different strains of intestinal bacteria cultured from humans have the ability to transform daidzein into (S)-equol or a related intermediate compound.[7] Several studies indicate that only 25 to 30 percent of the adult population of Western countries produces (S)-equol after eating soy foods containing isoflavones,[11][12][13][14] significantly lower than the reported 50 to 60 percent frequency of equol-producers in adults from Japan, Korea, or China.[15][16][17][18] Vegetarians are more capable of transforming daidzein in this substance too.[19] In research studies, the ability of a person to produce (S)-equol is determined with a standardized test in which the person, who has not had antibiotics for at least a month prior to testing, drinks two 240 milliliter glasses of soy milk or eats a soy food equivalent for three days followed by measurement of (S)-equol concentrations in their urine on the test's fourth day.[20] Seaweed and dairy consumption enhances the production of equol.[11]

Pharmacology

Estrogen receptor binding

(S)-Equol has about 2% of the affinity for the human estrogen receptor alpha (ERα) estrogen compared to estradiol. (S)-Equol has a stronger affinity for the human estrogen receptor beta (ERβ), yet this affinity is still just 20% that of estradiol. The preferential binding of (S)-equol to ERβ, compared to ERα and to that of estradiol, indicates the molecule may share some of the characteristics of a selective estrogen receptor modulator (SERM).[21]

Pharmacokinetics

(S)-Equol is a very stable molecule that essentially remains unchanged when digested, and this lack of further metabolism explains its very quick absorption and high bioavailability.[22] When (S)-equol is consumed, it is rapidly absorbed and achieves a Tmax (rate of peak plasma concentration) in two to three hours. In comparison, the Tmax of the daidzein is 4 to 10 hours because it occurs in a glycoside (with a glucose (sugar) side chain) form and the body must, in order to use daidzein, convert daidzein to its aglycone form (without the glucose side chain), achieved through removal of the sugar during digestion. If consumed directly in aglycone form, daidzein has a Tmax of one to three hours.[23] Also, the percent fractional elimination of (S)-equol in urine after oral administration is extremely high and, in some adults, can be close to 100 percent, which is far higher than the percent fractional eliminations of either daidzein (30 to 40 percent) or genistein (7 to 15 percent).[24]

Equol has been found to act as an agonist of the GPER (GPR30).[25]

See also

References

  1. ↑ The structures of 7,4’-dihydroxy-isoflavan and its precursors is shown in Structural Elucidation of Hydroxylated Metabolites of the Isoflavan Equol by GC/MS and HPLC/MS by Corinna E. Rüfer, Hansruedi Glatt, and Sabine E. Kulling in Drug Metabolism and Disposition (2005, electronic publication).
  2. 1 2 Wang XL, Hur HG, Lee JH, Kim KT, Kim SI (January 2005). "Enantioselective synthesis of S-equol from dihydrodaidzein by a newly isolated anaerobic human intestinal bacterium". Appl. Environ. Microbiol. 71 (1): 214–9. doi:10.1128/AEM.71.1.214-219.2005. PMC 544246Freely accessible. PMID 15640190.
  3. ↑ Frankenfeld CL, Atkinson C, Thomas WK, et al. (December 2005). "High concordance of daidzein-metabolizing phenotypes in individuals measured 1 to 3 years apart". Br. J. Nutr. 94 (6): 873–6. doi:10.1079/bjn20051565. PMID 16351761.
  4. ↑ Setchell, Kenneth D. R.; Carlo Clerici (June 2, 2010). "Equol: history, chemistry, and formation". J Nutr. 140 (7): 1355S–62S. doi:10.3945/jn.109.119776. PMC 2884333Freely accessible. PMID 20519412. Retrieved 13 December 2011.
  5. ↑ Mueller SO, Simon S, Chae K, Metzler M, Korach KS (April 2004). "Phytoestrogens and their human metabolites show distinct agonistic and antagonistic properties on estrogen receptor {α} (ER{α}) and ERβ in human cells". Toxicol. Sci. 80 (1): 14–25. doi:10.1093/toxsci/kfh147. PMID 15084758.
  6. ↑ Marrian, GF; Haslewood, GA (1932). "Equol, a new inactive phenol isolated from the ketohydroxyoestrin fraction of mares' urine". The Biochemical Journal. 26 (4): 1227–32. doi:10.1042/bj0261227. PMC 1261026Freely accessible. PMID 16744928.
  7. 1 2 3 4 Setchell, KD; Clerici, C (July 2010). "Equol: history, chemistry, and formation". The Journal of Nutrition. 140 (7): 1355S–62S. doi:10.3945/jn.109.119776. PMC 2884333Freely accessible. PMID 20519412.
  8. ↑ Axelson, M; Kirk, DN; Farrant, RD; Cooley, G; Lawson, AM; Setchell, KD (1982-02-01). "The identification of the weak oestrogen equol [7-hydroxy-3-(4'-hydroxyphenyl)chroman] in human urine". The Biochemical Journal. 201 (2): 353–7. doi:10.1042/bj2010353. PMC 1163650Freely accessible. PMID 7082293.
  9. 1 2 Setchell, KD; Borriello, SP; Hulme, P; Kirk, DN; Axelson, M (September 1984). "Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease". The American Journal of Clinical Nutrition. 40 (3): 569–78. PMID 6383008.
  10. ↑ Setchell, KD; Brown, NM; Lydeking-Olsen, E (December 2002). "The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones". The Journal of Nutrition. 132 (12): 3577–84. PMID 12468591.
  11. 1 2 3 Atkinson, C; Frankenfeld, CL; Lampe, JW (March 2005). "Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health". Experimental Biology and Medicine (Maywood, N.J.). 230 (3): 155–70. PMID 15734719.
  12. ↑ Lampe, JW; Karr, SC; Hutchins, AM; Slavin, JL (March 1998). "Urinary equol excretion with a soy challenge: influence of habitual diet". Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine. 217 (3): 335–9. doi:10.3181/00379727-217-44241. PMID 9492344.
  13. ↑ Setchell, KD; Cole, SJ (August 2006). "Method of defining equol-producer status and its frequency among vegetarians". The Journal of Nutrition. 136 (8): 2188–93. PMID 16857839.
  14. ↑ Rowland, IR; Wiseman, H; Sanders, TA; Adlercreutz, H; Bowey, EA (2000). "Interindividual variation in metabolism of soy isoflavones and lignans: influence of habitual diet on equol production by the gut microflora". Nutrition and Cancer. 36 (1): 27–32. doi:10.1207/S15327914NC3601_5. PMID 10798213.
  15. ↑ Watanabe, S; Yamaguchi, M; Sobue, T; Takahashi, T; Miura, T; Arai, Y; Mazur, W; Wähälä, K; Adlercreutz, H (October 1998). "Pharmacokinetics of soybean isoflavones in plasma, urine and feces of men after ingestion of 60 g baked soybean powder (kinako)". The Journal of Nutrition. 128 (10): 1710–5. PMID 9772140.
  16. ↑ Arai, Y; Uehara, M; Sato, Y; Kimira, M; Eboshida, A; Adlercreutz, H; Watanabe, S (March 2000). "Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake". Journal of Epidemiology / Japan Epidemiological Association. 10 (2): 127–35. doi:10.2188/jea.10.127. PMID 10778038.
  17. ↑ Akaza, H; Miyanaga, N; Takashima, N; Naito, S; Hirao, Y; Tsukamoto, T; Fujioka, T; Mori, M; Kim, WJ; Song, JM; Pantuck, AJ (February 2004). "Comparisons of percent equol producers between prostate cancer patients and controls: case-controlled studies of isoflavones in Japanese, Korean and American residents". Japanese Journal of Clinical Oncology. 34 (2): 86–9. doi:10.1093/jjco/hyh015. PMID 15067102.
  18. ↑ Song, KB; Atkinson, C; Frankenfeld, CL; Jokela, T; Wähälä, K; Thomas, WK; Lampe, JW (May 2006). "Prevalence of daidzein-metabolizing phenotypes differs between Caucasian and Korean American women and girls". The Journal of Nutrition. 136 (5): 1347–51. PMID 16614428.
  19. ↑ Patisaul, HB; Jefferson, W (October 2010). "The pros and cons of phytoestrogens.". Front Neuroendocrinol. 31 (4): 400–419. doi:10.1016/j.yfrne.2010.03.003. PMC 3074428Freely accessible. PMID 20347861.
  20. ↑ Setchell, KD; Cole, SJ (August 2006). "Method of defining equol-producer status and its frequency among vegetarians". The Journal of Nutrition. 136 (8): 2188–93. PMID 16857839.
  21. ↑ Setchell, KD; Clerici, C; Lephart, ED; Cole, SJ; Heenan, C; Castellani, D; Wolfe, BE; Nechemias-Zimmer, L; Brown, NM; Lund, TD; Handa, RJ; Heubi, JE (May 2005). "S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora". The American Journal of Clinical Nutrition. 81 (5): 1072–9. PMID 15883431.
  22. ↑ Setchell, KD; Zhao, X; Jha, P; Heubi, JE; Brown, NM (Oct 2009). "The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers". The American Journal of Clinical Nutrition. 90 (4): 1029–37. doi:10.3945/ajcn.2009.27981. PMC 2744624Freely accessible. PMID 19710188.
  23. ↑ Setchell, KD; Zhao, X; Shoaf, SE; Ragland, K (Nov 2009). "The pharmacokinetics of S-(-)equol administered as SE5-OH tablets to healthy postmenopausal women". The Journal of Nutrition. 139 (11): 2037–43. doi:10.3945/jn.109.110874. PMID 19776178.
  24. ↑ Setchell, KD; Clerici, C (Jul 2010). "Equol: pharmacokinetics and biological actions". The Journal of Nutrition. 140 (7): 1363S–8S. doi:10.3945/jn.109.119784. PMC 2884334Freely accessible. PMID 20519411.
  25. ↑ Prossnitz, Eric R.; Barton, Matthias (2014). "Estrogen biology: New insights into GPER function and clinical opportunities". Molecular and Cellular Endocrinology. 389 (1-2): 71–83. doi:10.1016/j.mce.2014.02.002. ISSN 0303-7207.
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