The role of soy isoflavones in menopausal health

Clarkson, Thomas B.; Utian, Wulf H.; Barnes, Stephen; Gold, Ellen B.; Basaria, Shehzad; Asô, Takeshi; Kronenberg, Fredi; Frankenfeld, Cara L.; Cline, J. Mark; Landgren, B.-M.; Gallagher, J. Christopher; Weaver, Connie M.; Hodis, Howard N.; Brinton, Roberta Dı́az; Maki, Pauline M.; Setchell, Kenneth D.R.; Setchell, D. R.; Allmen, Tara I.; Messina, Mark; Shu, Xiao Ou; Ishimi, Yoshiko; Wong, William W.; Kim, Helen

doi:10.1097/gme.0b013e31821fc8e0

Cited by 129 publications

(52 citation statements)

References 215 publications

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“…Their actions in bone are believed to be mediated by binding to estrogen receptor (ER) α or β, which subsequently leads to the alteration of gene transcription via interaction with estrogen response elements (EREs) in the promoters of target genes [12]. However, concerns have been raised regarding the potential unintended side effects of soy isoflavones in other estrogen sensitive tissues [13]. On the other hand, the most commonly consumed flavonoids in both Western and Asian countries were flavan-3-ols, especially those found in tea.…”

Section: Introductionmentioning

confidence: 99%

(−)-Epiafzelechin Protects against Ovariectomy-induced Bone Loss in Adult Mice and Modulate Osteoblastic and Osteoclastic Functions In Vitro

et al. 2017

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The present study was designed to characterize the bone protective effects of (−)-epiafzelechin (EAF), a flavan-3-ol, in mature ovariectomized mice model and its ability to stimulate osteoblastic activity and inhibit osteoclastic activity. Mature C57BL/6 mice (three to four months old) were either ovariectomised (OVX) or sham-operated and subjected to treatment (vehicle, 17β-oestradiol (E2, 200 μg/kg/day) or EAF (500 μg/kg/day) orally for six weeks. EAF and E2 significantly reduced urinary calcium (Ca) excretion, serum osteocalcin (OCN), and urinary deoxy-pyridinoline (DPD); increased bone mineral density (BMD); and improved micro-architectural properties in OVX mice. EAF significantly increased cell viability, alkaline phosphatise (ALP) activity, and collagen content, as well as runt-related transcriptional factor 2 (Runx2) mRNA expression in murine osteoblastic MC3T3-E1 cells. In addition, EAF significantly reduced the viability of osteoclast precursor murine leukemia monocyte RAW 264.7 cells and tartrate-resistant acid phosphatase (TRAP) activities in mature osteoclastic RAW 264.7 cells. EAF is a bioactive flavan-3-ol that protects estrogen deficiency-induced bone loss in OVX mice and exerts direct modulating effects in bone cells in vitro.

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Section: Introductionmentioning

confidence: 99%

(−)-Epiafzelechin Protects against Ovariectomy-induced Bone Loss in Adult Mice and Modulate Osteoblastic and Osteoclastic Functions In Vitro

et al. 2017

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“…Supplements commonly contain soy protein which is a rich source of isoflavones; specifically genistein, daidzein, and glycitein. 5 …”

Section: Introductionmentioning

confidence: 99%

Effect of soy isoflavones on thyroid hormones in intact and ovariectomized cynomolgus monkeys (Macaca fascicularis)

Silverstein

Kaplan

Appt³

et al. 2014

Menopause

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Objectives Soy isoflavones are commonly used to alleviate menopause-related symptoms. Menopausal women are at an increased risk for hypothyroidism and there are concerns that isoflavones may be detrimental to thyroid health. The aim of this study was to examine the effects of soy protein and isoflavones on thyroid function and the relationship between thyroid and ovarian function. Methods Adult female cynomolgus monkeys (Macaca fascicularis) were randomized to consume two diets differing only in protein source: casein-lactalbumin (n = 44) or soy protein with isoflavones (n = 41). After 34 months all animals were ovariectomized via laparotomy. Half of the monkeys from each diet treatment group continued to consume their Pre-Ovariectomy treatment phase diet (either SOY [n = 19] or CL [n = 21]) for an additional 34 months. The remaining animals did not continue their diets, and thus were not considered further. Circulating progesterone, triiodothyronine, thyroxine, and thyroid stimulating hormone were measured at baseline. Thyroid hormones were remeasured during each treatment phase. Results Dietary soy increased triiodothyronine in pre-ovariectomized monkeys and prevented a decline in thyroxine following surgical menopause (both p’s < 0.05). Mean progesterone concentrations were positively correlated with triiodothyronine at baseline in pre-ovariectomized monkeys (p < 0.01). Conclusions Progesterone levels and triiodothyronine are positively correlated in macaques. Dietary soy increases triiodothyronine in pre-ovariectomized monkeys and prevents a decline in thyroxine following surgical menopause. The outcomes observed in this study suggest soy protein and isoflavone consumption does not adversely affect and may even preserve thyroid function in postmenopausal women.

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“…Preliminary studies have suggested that supplementation with purified soy isoflavones may improve cognitive performance, in both men and women (Gleason et al, 2009; Thorp et al, 2009). However, these studies were based on relatively small subject numbers and it remains uncertain whether soy isoflavone supplementation has beneficial effects, in larger human populations (Clarkson et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

Low dietary soy isoflavonoids increase hippocampal spine synapse density in ovariectomized rats

2017

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High dietary intake of plant estrogens (phytoestrogens) can affect brain structure and function. The effects of phytoestrogen intake within the range of normal animal and human dietary consumption, however, remain uncertain. The aim of the present study was to determine the effects of the isoflavonoids present in a standard low phytoestrogen laboratory rat chow on spine synapse density in the stratum radiatum of area CA1 of the hippocampus. Weanling rats (22 days old) were fed either standard chow (Teklad 2018), a nutritionally comparable diet without soy (Teklad 2016) or a custom diet containing Teklad 2016 supplemented with the principal soy isoflavonoids, daidzein and genistein, for 40 days. Rats were ovariectomized at 54 days of age. Eight days later, spine synapse density on the apical dendrites of hippocampal pyramidal neurons in the stratum radiatum of area CA1 was measured by electron microscopic stereological analysis. Animals maintained on Teklad 2016 exhibited an approximately 60% lower CA1 spine synapse density than animals consuming Teklad 2018. Replacing genistein and daidzein in Teklad 2016 returned synapse density to levels indistinguishable from those in animals on Teklad 2018. These results indicate that the isoflavonoids in a standard laboratory rat diet exert significant effects on spine synapse density in the CA1 region of the hippocampus. Since changes in spine synapse density in this region of the hippocampus have been linked to cognitive performance and mood state, these data suggest that even relatively low daily consumption of soy phytoestrogens may be sufficient to influence hippocampal function.

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The role of soy isoflavones in menopausal health

Cited by 129 publications

References 215 publications

(−)-Epiafzelechin Protects against Ovariectomy-induced Bone Loss in Adult Mice and Modulate Osteoblastic and Osteoclastic Functions In Vitro

(−)-Epiafzelechin Protects against Ovariectomy-induced Bone Loss in Adult Mice and Modulate Osteoblastic and Osteoclastic Functions In Vitro

Effect of soy isoflavones on thyroid hormones in intact and ovariectomized cynomolgus monkeys (Macaca fascicularis)

Low dietary soy isoflavonoids increase hippocampal spine synapse density in ovariectomized rats

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