Daidzein belongs to the group of isoflavones or isoflavonoids, which are classified as secondary plant compounds (bioactive substances with health-promoting effects – “anutritive ingredients”). Chemically, daidzein is derived from polyphenols – a disparate group of substances based on the structure of phenol (a compound with an aromatic ring and one or more attached hydroxyl (OH) groups). Daidzein is a 3-phenylchroman derivative that has two OH groups attached – 4′,7-dihydroxyisoflavone. Daidzein has structural similarities with the steroid hormone 17ß-estradiol (female sex hormone) and thus has the ability to bind to estrogen receptors (ER), especially ER-ß receptors – type II estrogen receptors – and block them for endogenous (endogenous) 17ß-estradiol by competitive inhibition. Accordingly, daidzein exerts an antiestrogenic effect in adult premenopausal women (women before menopause) with high estrogen levels, whereas the isoflavone develops a more estrogenic effect in childhood up to puberty and in postmenopausal women (women after menopause) in whom estrogen levels are lowered [1-3, 8, 10, 18, 20]. Daidzein is also called a phytoestrogen for this reason. However, its hormonal activity is lower by a factor of 100 to 1,000 compared to that of 17ß-estradiol produced in the mammalian organism. However, the concentration of daidzein in the body can be several times higher than that of the endogenous (endogenous) hormone [1-3, 8, 10, 12, 13, 18, 20]. Because daidzein induces (triggers) both estrogenic and antiestrogenic effects, it is classified as a natural SERM (Selective Estrogen Receptor Modulator). Selective estrogen receptor modulators, such as raloxifene (drug used to treat osteoporosis), inhibit ER-alpha receptors located primarily in the breast, endometrium (lining of the uterus), ovaries (ovaries), and hypothalamus (section of the diencephalon), and at the same time stimulate ER-ß receptors, which are found in kidney, brain, bone, heart, lung, intestinal mucosa (intestinal mucosa), prostate, and endothelium (cells of the innermost wall layer of lymph and blood vessels facing the vascular lumen). SERMs thus act in a tissue-specific manner and show estrogen-like effects on bone, for example (→ prevention of osteoporosis (bone loss)), whereas estrogen effects are antagonized (inhibited) in breast and uterus (womb) (→ inhibition of hormone-associated tumor growth).
Synthesis
Daidzein is synthesized (produced) exclusively by plants, especially tropical legumes (pulses). The quantitatively (quantitatively) most significant amount of daidzein is contained in soybean with 20-52 mg/100 g, followed by soy milk with 1-13 mg/100 g and tofu with 7-11 mg/100 g. In the plant organism, isoflavone is predominantly present in bound form as glycoside (binding to glucose) – daidzin – and only to a small extent in free form as aglycone (without sugar binding) – daidzein. In fermented soy products, such as tempeh, miso, and soybean paste, on the other hand, daidzein is found primarily as an aglycone.
Absorption
Dietary free and glycosidically bound daidzein enter the small intestine for absorption. While unbound daidzein is absorbed into enterocytes (cells of the small intestinal epithelium) via passive diffusion, daidzein glycosides are first hydrolyzed by glycosidases (enzymes that break down glucose molecules by reacting with water) at the brush border membrane of epithelial cells for subsequent passive absorption as free daidzein. Absorption of glycosidically bound daidzein can also occur in an intact form via the sodium/glucose cotransporter-1 (SGLT-1), which transports glucose and sodium ions into the cell by means of a symport (same-direction transport). Aglycone and glycoside forms of daidzein not absorbed in the small intestine are taken up in the colon (large intestine) by passive diffusion into the mucosa cells (mucosal cells) to a small extent after hydrolysis of the daidzein glycosides by bacterial beta-glucosidases (enzymes that cleave glucose molecules by reaction with water).The majority of free daidzein is converted by microbial enzymes into O-demethylangolensin and equol (4′,7-isoflavandiol) and absorbed in this form.The formation of equol depends on the composition of the colon flora and is subject to strong individual variations. The bacterial strains responsible for equol synthesis have not yet been clearly identified. Streptococci, lactobacilli (lactic acid bacteria) and bifidobacteria are under discussion. Only about 30-50 % of people are able to produce equol from daidzein – this is significant because equol has a high binding affinity to estrogen receptors, especially to the ER-ß receptors. Its activity is about 50% that of 17ß-estradiol [1-3, 5, 7, 8, 14, 20, 21, 22, 25]. Therapy with antibiotics can significantly decrease equol synthesis by affecting the colon flora. The bioavailability of daidzein ranges from 13-35%. Studies on the biokinetics of daidzein aglycones and glycosides have shown that the aglycones are absorbed more rapidly than the glycoside derivatives. The extent to which the total availability of free and glycoside-bound daidzein differs has not been conclusively determined.
Transport and distribution in the body
Absorbed daidzein and its metabolites enter the liver via the portal vein and are transported from there to organs and tissues. Little is known to date about the distribution and storage of daidzein in the human body. Studies with rats administered radiolabeled isoflavones have shown that they are preferentially stored in mammary tissue, ovaries (ovaries), and uterus (uterus) in females and in the prostate gland in males. In the intervention study by Bolca et al with healthy women, a 40:60 distribution of isoflavones in the fatty and glandular tissues of the breast, respectively, was observed after ingestion of soy milk and soy supplements. In tissues and organs, 50-90% of daidzein is present as aglycone, the biologically active form. In blood plasma, on the other hand, an aglycone content of only 1-2 % is detectable. The isoflavone plasma concentration is about 50 nmol in an average mixed diet, while this can increase to about 870 nmol with a diet rich in soy products. The maximum isoflavone concentration in blood plasma was reached approximately 6.5 hours after the intake of soy products. After 24 hours, virtually no levels were detectable.
Excretion
To convert daidzein into an excretable form, it undergoes biotransformation.Biotransformation occurs in the liver and can be divided into two phases:
- In phase I, daidzein is hydroxylated (insertion of an OH group) by the cytochrome P-450 system to increase solubility.
- In phase II, conjugation with highly hydrophilic (water-soluble) substances takes place – for this purpose, glucuronic acid, sulfate and the amino acid glycine are transferred to the previously inserted OH group of daidzein with the help of enzymes
The conjugated daidzein metabolites are excreted primarily by the kidneys and to a lesser extent by the bile. Biliary (“affecting the bile“) secreted (secreted) daidzein is metabolized (metabolized) in the colon (large intestine) by the enzymes of the intestinal flora and reabsorbed. Thus, similar to endogenous (endogenous) steroid hormones, the phytoestrogen is subject to enterohepatic circulation (liver–gut circulation).
