Equol

Template:Short description Template:Chembox Equol (4',7-isoflavandiol) is an isoflavandiol<ref name="structure">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).</ref> estrogen metabolized from daidzein, a type of isoflavone found in soybeans and other plant sources, by bacterial flora in the intestines.<ref name="bacteria">Template:Cite journal</ref><ref name="MuthyalaJu2004">Template:Cite journal</ref> While endogenous estrogenic hormones such as estradiol are steroids, equol is a nonsteroidal estrogen. Only about 30–50% of people have intestinal bacteria that make equol.<ref name="percent">Template:Cite journal</ref>

HistoryEdit

(S)-Equol was first isolated from horse urine in 1932,<ref>Template:Cite journal</ref> and the name was suggested by this equine connection.<ref name= Setchell >Template:Cite journal</ref> Since then, equol has been found in the urine or plasma of many other animal species, although these animals have significant differences in their ability to metabolize daidzein into equol.<ref name= Setchell/> In 1980, scientists reported the discovery of equol in humans.<ref>Template:Cite journal</ref> 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.<ref name=pmid6383008>Template:Cite journal</ref>

Chemical structureEdit

Equol is a compound that can exist in two mirror-image forms known as enantiomers: (S)-equol and (R)-equol. (S)-equol is produced in humans and animals with the ability to metabolize the soy isoflavone daidzein, while (R)-equol can be chemically synthesized.<ref>Template:Cite journal</ref> The molecular and physical structure of (S)-equol is similar to that of the hormone estradiol.<ref name="pmid15734719">Template:Cite journal</ref> (S)-Equol preferentially binds estrogen receptor beta.<ref name="bacteria" /><ref name="receptors">Template:Cite journal</ref>

PharmacologyEdit

Estrogen receptor bindingEdit

(S)-equol is a nonsteroidal, selective agonist of ERβ (K_i = 16 nM) with 13-fold selectivity for ERβ over ERα.<ref name="MuthyalaJu2004" /> Relative to (S)-equol, (R)-equol is less potent and binds to ERα (K_i = 50 nM) with 3.5-fold selectivity over ERβ.<ref name="MuthyalaJu2004" /> (S)-Equol has about 2% of estradiol's binding affinity for human estrogen receptor alpha (ERα) and 20% of estradiol's binding affinity for human estrogen receptor beta (ERβ). The preferential binding of (S)-equol to ERβ vs. ERα and in comparison to that of estradiol suggests the molecule may share some of the characteristics of a selective estrogen receptor modulator (SERM).<ref>Template:Cite journal</ref> Equol has been found to act as an agonist of the GPER (GPR30).<ref name="ProssnitzBarton2014">Template:Cite journal</ref>

PharmacokineticsEdit

(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.<ref>Template:Cite journal</ref> When (S)-equol is consumed, it is rapidly absorbed and achieves a T_max (rate of peak plasma concentration) in two to three hours. In comparison, the T_max of daidzein is 4 to 10 hours because daidzein exists in glycoside (with a glucose side chain) form. The body must convert daidzein to its aglycone form (without the glucose side chain) via removal of the sugar side chain during digestion before it can use daidzein. If consumed directly in aglycone form, daidzein has a T_max of one to three hours.<ref>Template:Cite journal</ref> The percent fractional elimination of (S)-equol in urine after oral administration is high and in some adults can reach close to 100 percent. The percent fractional elimination of daidzein is much lower at 30 to 40 percent.<ref>Template:Cite journal</ref>

Production in humansEdit

To produce (S)-equol after soy consumption, humans must have certain strains of bacteria living within their intestines.<ref name=pmid6383008/> Twenty-one different strains of intestinal bacteria cultured from humans have been shown to have the ability to transform daidzein into (S)-equol or a related intermediate compound.<ref name= Setchell/> Several studies indicate that only 25 to 30 percent of the adult populations of Western countries produce (S)-equol after eating soy foods containing isoflavones,<ref name=pmid15734719/><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> while 50 to 60 percent of adults from Japan, Korea, and China are equol-producers.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Vegetarians have also been reported to be more capable of transforming daidzein into (S)-equol.<ref>Template:Cite journal</ref> Seaweed and dairy consumption can enhance the production of equol.<ref name="pmid15734719" /><ref>Template:Cite journal</ref> The ability of a person to produce (S)-equol is determined by testing people who have not taken any antibiotics for at least a month. For this standardized test, the individual drinks two 240 milliliter glasses of soy milk or eats a soy food equivalent for three days. The (S)-equol concentration in each test subject's urine is determined on day four.<ref>Template:Cite journal</ref>

Equol producing bacteriaEdit

While many more bacteria are involved in the related intermediate process of equol production, such as conversion of daidzin to daidzein, or genistein to 5-Hydroxy-equol, the bacteria that achieve the complete conversion of daidzein to (S)-equol,<ref name="pmid15883431">Template:Cite journal</ref> include:<ref>Template:Cite journal</ref>

Conversion by Bifidobacterium has only been reported once by Tsangalis et al. in 2002<ref>Template:Cite book</ref> and not reproduced since.Bifidobacteria: Genomics and Molecular Aspects Mixed cultures such as Lactobacillus sp. Niu-O16 and Eggerthella sp. Julong 732 can also produce (S)-equol.Bifidobacteria: Genomics and Molecular Aspects Some equol producing bacteria, as implied by their nomenclature, are Adlercreutzia equolifaciens, Slackia equolifaciens and Slackia isoflavoniconvertens.

Health effectsEdit

Skin healthEdit

The topical effects of equol as an anti-aging substance have been shown in different studies. The effects result from both molecular and structural changes to the skin. Equol can, for instance, lead to an increase in telomere length. As an antioxidant, equol can decrease the aging process by reducing damage caused by reactive oxygen species (ROS). It may also act as a protective anti-photoaging substance by inhibiting acute UVA- induced lipid peroxidation.<ref>Reeve V, Widyarini S, Domanski D, Chew K, Barnes K. Protection Against Photoaging in the Hairless Mouse by the Isoflavone Equol. Photochemistry and Photobiology, Volume 81, Issue 6, November 2005, Pages 1548-1553</ref> In addition, equol may have a positive impact on epigenetic regulation.<ref>Template:Cite journal</ref> Equol's phytoestrogenic properties may also affect skin health.<ref name="pmid27521253">Template:Cite journal</ref> Reduction of dark circles and eye wrinkles after treatment with equol has been reported.<ref>Urbanek C, Haslberger A, Hippe B, Gessner D, Fiala H, Equol – a Topically Applied Phyto-Oestrogen Improves Skin Characteristics. Global ingredients and Formulations Guide 2016</ref> Equol may also protect skin from damage by pollution due to its anti-oxidative and anti-inflammatory properties.<ref>Template:Cite journal</ref>

Each of the enantiomers and the racemic mixture of both enantiomers have different characteristics, bioavailabilities and molecular effects.<ref name="Lephart 1393–1400">Template:Cite journal</ref> According to one study, (RS)-equol provided the greatest overall improvement in skin health, especially when applied topically.<ref name="Lephart 1393–1400"/>

Hormone-related health effectsEdit

Beyond topical effects, medicinal equol has been shown to relieve menopausal symptoms such as hot flashes and muscle and joint pain.<ref>Efficacy and safety of natural S-equol supplement in US postmenopausal women. Belinda H. Jenks of Scientific Affairs, Pharmavite LLC, Northridge, CA, et.al.</ref><ref>Effect of natural S-equol on bone metabolism in equol non-producing postmenopausal Japanese women: a pilot randomized placebo-controlled trial. Tomomi Ueno of Saga Nutraceutricals Research Institute, Otsuka Pharmaceutical Co., Ltd., Japan, et.al</ref> (RS)-equol was also reported to reduce symptoms associated with menopausal vaginal atrophy, such as vaginal itching, vaginal dryness and pain with intercourse and cause positive shifts in the vaginal bacterial population, cell composition, and pH.<ref>Template:Cite journal</ref>

According to animal studies,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> it has anti-androgenic effects and may lead to inhibited 5-alpha reductase as well as lowered dihydrotestosterone (DHT) levels.

ReferencesEdit

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Template:Phytoestrogens Template:Estrogenics Template:Isoflavane Template:Soy