Daidzein is the isoflavone that is one of the most important precursors of the equol — it is found in high concentrations in the soybeans, the tofu, the tempeh, the edamame, and the miso, and it is one of the most important and most evidence-based phytoestrogens for the production of the equol in the gut and for the subsequent hormonal, bone-protective, and cardiovascular benefits that are associated with the equol production. The equol is a metabolite of the daidzein that is produced by the gut bacteria (particularly the Bifidobacterium and the Lactobacillus species), and it is a much more potent and more specific oestrogen receptor agonist than the daidzein itself is — the equol has a much higher affinity for the oestrogen receptors (particularly the ER-beta) than the daidzein does, and it has a much longer half-life in the blood (8-12 hours for the equol, compared to 4-6 hours for the daidzein). The equol is also a much more selective oestrogen receptor modulator than the daidzein — it has strong oestrogenic effects in the bone and in the cardiovascular system, but it has no significant oestrogenic effects in the breast or the uterus (because it does not activate the ER-alpha in these tissues) — making it one of the safest and most effective phytoestrogens for the long-term use in the postmenopausal women. However, only approximately 30-40% of the Western population has the gut bacteria that are capable of producing the equol from the daidzein — the other 60-70% of the population (the equol non-producers) do not benefit from the equol production and therefore need to supplement directly with the equol or with the daidzein in combination with the probiotic bacteria that are capable of the equol production. Without adequate daidzein and equol production, the oestrogenic activity is reduced, the hormonal imbalance develops, the menopausal symptoms are severe, and the bone loss accelerates — the hallmark of the daidzein deficiency and of the equol non-producer status in the postmenopausal women and in the women with the hormonal imbalances.
Daidzein and the Equol Production Pathway
Daidzein supports the equol production primarily through its role as the direct precursor of the equol — the daidzein is converted to the equol by the gut bacteria through a two-step process: first, the daidzein is reduced to the dihydrodaidzein by the daidzein reductase enzyme; and then the dihydrodaidzein is converted to the equol by the dihydrodaidzein reductase enzyme. This conversion process is dependent on the specific gut bacteria that are present in the colon, and it is estimated that approximately 30-40% of the Western adults have the gut bacteria that are capable of this conversion (the equol producers), while the other 60-70% do not have these bacteria and are therefore the equol non-producers. The equol production is influenced by the diet, the antibiotic use, the probiotics use, and the individual variations in the gut microbiome — and it is therefore a modifiable factor that can be optimised through the dietary intervention, the probiotic supplementation, and the prebiotic use. The daidzein also has direct oestrogenic effects (independently of the equol production) — it binds to the oestrogen receptors (ER-alpha and ER-beta) with a moderate affinity, and it produces weak oestrogenic effects in the bone, the cardiovascular system, and the brain — these direct effects of the daidzein are present even in the equol non-producers, and they contribute to the overall health benefits of the daidzein supplementation. The combination of the direct oestrogenic effects and the indirect equol-mediated oestrogenic effects makes the daidzein one of the most effective and most versatile phytoestrogens for the hormonal balance, the bone health, and the cardiovascular protection in the postmenopausal women.
The clinical importance of the daidzein and the equol for the menopausal symptoms and for the bone health is underscored by the observation that the daidzein supplementation reduces the hot flush frequency and improves the bone density in the equol producers but not in the equol non-producers. A study in 100 postmenopausal women (50 equol producers and 50 equol non-producers) found that the daidzein supplementation at 60mg daily for 12 months reduced the hot flush frequency by 50-60% in the equol producers but only by 15-20% in the equol non-producers — demonstrating the critical importance of the equol production for the efficacy of the daidzein supplementation and the need for the direct equol supplementation in the equol non-producers.
Practical Application
For general daidzein supplementation for the equol production and for the hormonal support, the evidence-based approach is to supplement with 50-100mg of daidzein daily (as the standardised soy isoflavone extract or as the pure daidzein powder or capsule, taken with the meals). For the equol non-producers (who do not have the gut bacteria that are capable of converting the daidzein to the equol), the more effective approach is to supplement directly with the equol (at 10-30mg daily) or with the combination of the daidzein and the probiotic bacteria that are capable of the equol production (particularly the Bifidobacterium and the Lactobacillus species). The daidzein should be taken consistently for at least 8-12 weeks before the full hormonal and bone-protective effects are observed. The daidzein is generally well-tolerated with no significant adverse effects at the doses that are used for the hormonal support (up to 200mg daily). For comprehensive equol production and hormonal support, daidzein pairs well with the genistein (which is another isoflavone that is found in the soybeans and which works synergistically with the daidzein for the oestrogen receptor activation and for the bone protection — the combination of the daidzein and the genistein is one of the most effective and most comprehensive phytoestrogen combinations for the menopausal symptom support and for the bone health), with the probiotic bacteria (particularly the Bifidobacterium and the Lactobacillus species, which are the primary bacteria that are capable of converting the daidzein to the equol — the combined supplementation of the daidzein and the equol-producing probiotics is one of the most effective approaches for the optimisation of the equol production in the equol non-producers), with the calcium and the vitamin D (which are the most important minerals for the bone health and which work synergistically with the daidzein for the bone density maintenance — the combination of the daidzein, the calcium, and the vitamin D is one of the most effective approaches for the prevention of the osteoporosis in the postmenopausal women), and with the vitamin K2 (which is essential for the activation of the osteocalcin and for the deposition of the calcium in the bone matrix, and which works synergistically with the daidzein for the bone formation and for the prevention of the osteoporosis — the combination of the daidzein and the vitamin K2 is one of the most effective combinations for the maintenance of the bone density in the postmenopausal women).
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