Equol (4',7-isoflavandiol) is an isoflavandiol estrogen metabolized from daidzein, a type of isoflavone found in soybeans and other plant sources, by bacterial flora in the intestines. 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.
History
(S)-Equol was first isolated from horse urine in 1932, and the name was suggested by this equine connection. 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. In 1980, scientists reported the discovery of equol in humans. 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.
Chemical structure
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. The molecular and physical structure of (S)-equol is similar to that of the hormone estradiol. (S)-Equol preferentially binds estrogen receptor beta.
Pharmacology
Estrogen receptor binding
(S)-equol is a nonsteroidal, selective agonist of ERβ (Ki = 16 nM) with 13-fold selectivity for ERβ over ERα. Relative to (S)-equol, (R)-equol is less potent and binds to ERα (Ki = 50 nM) with 3.5-fold selectivity over ERβ. (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). Equol has been found to act as an agonist of the GPER (GPR30).
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. 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 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 Tmax of one to three hours. 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.
Production in humans
To produce (S)-equol after soy consumption, humans must have certain strains of bacteria living within their intestines. 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. 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, while 50 to 60 percent of adults from Japan, Korea, and China are equol-producers. Vegetarians have also been reported to be more capable of transforming daidzein into (S)-equol. Seaweed and dairy consumption can enhance the production of equol. 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.