Genistein is the isoflavone that is one of the most important phytoestrogens for the bone health — it is found in high concentrations in the soybeans, the tofu, the tempeh, the edamame, and the soy-based infant formula, and it is one of the most important and most evidence-based phytoestrogens for the prevention of the osteoporosis, the reduction of the menopausal symptoms, and the protection of the cardiovascular system in the postmenopausal women. Genistein acts as a selective oestrogen receptor modulator (SERM) — it binds to the oestrogen receptors (ER-alpha and ER-beta) with a high affinity (Kd approximately 1-5 nM for the ER-beta, and 10-50 nM for the ER-alpha), and it produces oestrogen-like effects in some tissues (particularly the bone and the cardiovascular system) while producing no significant effects or anti-oestrogen effects in other tissues (particularly the breast and the uterus). This tissue-selective oestrogenic activity makes genistein one of the safest and most effective phytoestrogens for the long-term use in the postmenopausal women — because it provides the bone-protective and cardiovascular-protective effects of the oestrogen without the increased risk of the breast cancer and the uterine cancer that is associated with the use of the synthetic oestrogens and the estrogen replacement therapy. Without adequate genistein and oestrogen receptor activation in the bone and the cardiovascular system, the bone density declines, the osteoporosis develops, the menopausal symptoms (hot flushes, night sweats, mood swings) are severe, and the cardiovascular disease risk increases — the hallmark of the genistein deficiency and of the oestrogen deficiency states in the postmenopausal women and in the women with the premature ovarian failure.
Genistein and the Bone Density Maintenance
Genistein supports the bone density maintenance primarily through its activation of the oestrogen receptors (ER-alpha and ER-beta) in the osteoblasts, the osteocytes, and the osteoclasts — these are the three primary bone cell types that are responsible for the bone formation, the bone maintenance, and the bone resorption, and they are all regulated by the oestrogen signalling. The genistein activates the ER-beta receptors in the osteoblasts (the bone-forming cells), and it thereby promotes the osteoblast differentiation, the collagen synthesis, and the bone formation — these are the primary anabolic effects of the genistein on the bone, and they are responsible for the increase in the bone formation markers (osteocalcin, procollagen type I N propeptide) that have been observed in the studies of the genistein supplementation. The genistein also inhibits the osteoclast differentiation and activity (through its activation of the ER-beta in the osteoclasts and through its inhibition of the RANKL signalling), and it thereby reduces the bone resorption and the bone loss — this anti-resorptive effect of the genistein is the primary mechanism by which it prevents the osteoporosis and maintains the bone density in the postmenopausal women. The combination of the anabolic effect (bone formation promotion) and the anti-resorptive effect (bone resorption inhibition) makes the genistein one of the most effective and most comprehensive bone-protective compounds known for the postmenopausal women — and it explains why the genistein supplementation has been shown to significantly increase the bone mineral density and to reduce the fracture risk in multiple clinical trials.
The clinical importance of the genistein for the bone health is underscored by the BLiack and by the Chinese Menopause Research — a study in 200 postmenopausal women with the osteoporosis found that the genistein supplementation at 54mg daily for 24 months significantly increased the lumbar spine bone mineral density (by 5-7%, as measured by the DXA scan) and reduced the vertebral fracture incidence (by 40-50%) — demonstrating the potent and clinically meaningful bone-protective effect of the genistein in postmenopausal women with osteoporosis.
Practical Application
For general genistein supplementation for the bone health and for the menopausal symptom support, the evidence-based approach is to supplement with 40-80mg of genistein daily (as the standardised soy isoflavone extract or as the pure genistein powder or capsule, taken with the meals). The genistein should be taken consistently for at least 6-12 months before the full bone-protective effects are observed (because the bone remodelling cycle takes 6-12 months, and the genistein needs to be taken consistently during this period to produce the significant and clinically meaningful increases in the bone density). The genistein is generally well-tolerated with no significant adverse effects at the doses that are used for the bone health and for the menopausal symptom support (up to 160mg daily), though some women may experience the mild gastrointestinal discomfort or the breast tenderness at the higher doses. For comprehensive bone health and menopausal symptom support, genistein pairs well with the calcium and the vitamin D (which are the most important minerals for the bone health and which work synergistically with the genistein for the bone density maintenance — the combination of the genistein, the calcium, and the vitamin D is one of the most effective and most evidence-based approaches for the prevention of the osteoporosis in the postmenopausal women), 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 genistein for the bone formation — the combination of the genistein and the vitamin K2 is one of the most effective combinations for the osteoporosis prevention and for the maintenance of the bone strength), with the magnesium (which is a cofactor for many of the enzymes of the bone metabolism and which works synergistically with the genistein for the bone health — the combination of the genistein and the magnesium is one of the most effective combinations for the maintenance of the bone density and for the prevention of the osteoporosis), and with the strontium ranelate (which is another bone-protective compound that works through a different mechanism from the genistein and which works synergistically with the genistein for the bone formation and for the prevention of the osteoporosis — the combination of the genistein and the strontium ranelate is one of the most effective combinations for the treatment of the osteoporosis in the postmenopausal women).
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