Bacterial metabolites of isoflavones forming in the gut. They also note that the effects of isoflavones are greater when administered as aglycones. Accessibility In addition, Qiu et al. National Library of Medicine In general terms, caution should be exercised with the use of high doses of isoflavones in women with a family history of breast cancer [49]. Regarding breast cancer (Table 4), the same increase in soy isoflavone intake (10 mg/day) was related to a 9% lower risk of breast cancer mortality. Lu D., Gigure V. Requirement of Ras-dependent pathways for activation of the transforming growth factor beta3 promoter by estradiol. The results showed no significant association between isoflavone consumption and gastric cancer risk, with the highest (0.675.5 mg/day) versus the lowest (0.0120.1 mg/day) categories of dietary isoflavone intake. Moreover, even though the binding affinity of isoflavones to the ER receptors is less than that of 17-estradiol, they can also act as estrogenic compounds when the endogenous estradiol is not available [8]. This difference could explain the slow effect of isoflavones in alleviating hot flushes. Contrary to other types of renewable energies, such as wind and hydroelectricity, evidence on the effects of PV panels on biodiversity has been building up only fairly recently. government site. The six meta-analyses show a slight improvement in the frequency and intensity of hot flushes. Thus, soybean can be considered as the best food source. Zhang Q., Feng H., Qluwakemi B., Wang J., Yao S., Cheng G., Xu H., Qiu H., Zhu L., Yuan M. Phytoestrogens and risk of prostate cancer: An updated meta-analysis of epidemiologic studies. Li L., Lv Y., Xu L., Zheng Q. Quantitative efficacy of soy isoflavones on menopausal hot flashes. In addition, several studies have observed that the urine excretion of daidzein metabolites is notably higher than that of genistein metabolites [44,45,46]. In this sense, the authors suggested that the composition of the gut microflora may influence isoflavone absorption and metabolism and could affect the production of isoflavone metabolites, which, in turn, could mediate their biological activity. Indeed, they reported that an increase of 10 mg/day of soy isoflavones consumption was associated with a 7% lower risk of cancer mortality [62]. This fact does not seem to be influenced by genetics since migrating from eastern to western countries appears to cause the loss of this protective effect. (2019) studied whether equol supplementation could benefit equol nonproducer subjects in lowering the incidence and severity of hot flushes [85]. Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in Korean women but not men: Results from the Korean Genome and Epidemiology Study. A total of 16 studies were included in their meta-analysis with a range of 24 to 236 subjects. Modified from Mace et al. FOIA Vasomotor symptoms resulting from natural menopause: A systematic review and network meta-analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause. Modified from Wang et al., 2006 [4]. While a moderate intake of soy isoflavones did not significantly affect breast cancer risk, a significant reduction was shown when the intake was high. The tides are crucial to life: tidal pools, sheltered and renewed in rhythm with these cycles, catalyzed some of the first stable ecologies and still represent unique niches. The dose of isoflavones ranged from 30 to 200 mg/day. Hormone replacement therapy has been proven to be effective in reducing vasomotor symptoms, although isoflavones have gained popularity as an alternative treatment to hormone replacement therapy to relieve menopausal symptoms. . Setchell K.D., Brown N.M., Lydeking-Olsen E. The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones. According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. The authors indicated that no consensus was found regarding the protective effects of soy isoflavones (2080 mg) and equol (10 mg) on bone resorption. Chadha R., Bhalla Y., Jain A., Chadha K., Karan M. Dietary Soy Isoflavone: A Mechanistic Insight. van der Schouw Y.T., Kreijkamp-Kaspers S., Peeters P.H., Keinan-Boker L., Rimm E.B., Grobbee D.E. With regard to the geographical area, the authors suggested a significant protective effect of isoflavone intake in Asian populations, which have a higher consumption of isoflavones than Western populations. Indeed, Kim and Je (2017) indicated that a high intake of flavonoids is associated with a reduced risk of mortality from cardiovascular diseases in men and women [56]. Gut bacterial metabolism of the soy isoflavone daidzein: Exploring the relevance to human health. Moreover, the number of publications grouping women according to pre- or post-diagnosis intake criteria is small. They observed that it was dose-dependent at low to moderate soybean consumption. The authors suggested that further studies grouping subjects by isoflavone intake or by the circulating isoflavone levels might enhance this association. Liu J., Yuan F., Gao J., Shan B., Ren Y., Wang H., Gao Y. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. They observed that daidzein and genistein intakes were associated with a significant reduction of prostate cancer risk. Taken as a whole, all these results suggest that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Scientists often disagree about certain things. Furthermore, isoflavones are associated with proteins; thus, alcohol extraction and processing diminish isoflavone content in foodstuffs such as fermented soybean, tofu or soy beverages. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. For the development of this section, the meta-analyses and systematic reviews published between 2015 and 2020 were taken into account. In this sense, it has been described that both isoflavones and other estrogenic molecules could mediate their beneficial effects due to two different mechanisms: the classical estrogen receptor (ER)-mediated signaling pathway and the activation of intracellular pathways such as protein tyrosine kinase, phospholipase C and mitogen-activated protein kinase (MAPK) [5,6]. Sirotkin A.V., Harrath A.H. Phytoestrogens and their effects. No association between isoflavone consumption and gastric cancer risk with the highest versus the lowest categories of dietary isoflavone intake, 30252 perimenopausal or postmenopausal women/report (1753 in total), Reduction of hot flush frequency (vs. placebo), Slight and slow attenuation of hot flushes (vs. estradiol), Slight and slow attenuation of hot flushes (vs. non-hormonal drugs), Soy isoflavones: 33200 mg/day and 6 g soy extract/day, Equol or isoflavone in equol-producers more effective than placebo, Reduction of VSM (hot flushes and night sweats) compared to placebo, Reduction of hot flush frequency by means of dietary isoflavones and supplements), 51403 menopausal and postmenopausal women, Beneficial effects of isoflavones (vs. placebo), 40403 menopausal and postmenopausal women. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level. Some gardening folklore suggests that planting crops according to the phases of the moon will give you a better harvest, but there is little scientific evidence to back this up. In: Thompson M.J., editor. In this line, another meta-analysis, which included 52 controlled trials and 5313 patients, shows that soy isoflavones have beneficial effects on bone mineral density in the femur neck, lumbar spine, and hip, regardless of body weight or ethnicity [49]. Possible mechanism of action of isoflavones for menopausal symptoms. In addition, genistein and glycitein are transformed into dihydrogenistein and dihydroglycitein, respectively, before being further converted into other metabolites. The Sun ruled our heart, blood circulation and spine, while the Moon had influence on growth, fertility, breasts, stomach, uterus and menstrual flow. In this line, three meta-analyses were conducted to study isoflavone consumption and endometrial cancer risk. Akhlaghi M., Ghasemi Nasab M., Riasatian M., Sadeghi F. Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials. This fact was not taken into account in previous meta-analyses, and thus it may justify the discrepancies amongst them. ; WritingReview and Editing, M.P.P., S.G.-Z., I.E. Equol is produced from the isoflavone daidzein by intestinal bacteria, mainly in the large intestine. Chalvon-Demersay T., Azzout-Marniche D., Arfsten J., Egli L., Gaudichon C., Karagounis L.G., Tom D. A Systematic Review of the Effects of Plant Compared with Animal Protein Sources on Features of Metabolic Syndrome. Opposite effect in Asian women, Prospective studies (3) Case-control studies (5), Isoflavone consumption (>45 mg/day among the Asian population, and >1 mg/day among the non-Asian population), Potential reduction risk associated with isoflavone consumption, Prospective cohort study (5) Case-control study (7), Cohort prospective study (2 studies from Japan and 5 studies from Europe), 241 cases and 503 controls (from Japanese studies), and 2828 cases and 5593 controls (from European studies), Circulating isoflavone concentrations (nmol/L): Daidzein (Japanese: 115166; European: 2.843.96), Genistein, daidzein and equol did not affect prostate cancer risk in both Japanese and European men, Case-control study (15) Cohort study (8) Nested case-control study (7), 266,699 (21,612 patients with prostate cancer), Isoflavones were not associated with a reduction of prostate cancer risk, Daidzein, genistein, and equol (dose not defined), 19% reduction in prostate cancer risk was found at high concentrations of daidzein, but not with genistein or equol, Participants: 11,346 cases and 140,177 controls, Daidzein and genistein intakes were associated with a reduction of prostate cancer risk (no effect with equol), 559,486 (among them 16,917 colorectal cancer cases), Foods rich in isoflavones (dose not defined), Soy foods (30 mg/day170 g/day) and isoflavones (0.01460 mg/day). Wang X., Dykens J.A., Perez E., Liu R., Yang S., Covey D.F., Simpkins J.W. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. The main isoflavones found in foodstuffs are daidzein, genistein and glycitein, as well as biochanin A and formononetin [9,12]. In this regard, it has been reported that isoflavones have a higher affinity to the -estrogen receptor [7], which, contrary to the -estrogen receptor, inhibits cell proliferation and stimulates apoptosis [84]. The enhanced bone formation is due to the stimulation of osteoblastic activity mainly through (a) the activation of estrogen receptors because they bind to nuclear estrogen receptors and exhibit estrogenic activity due to its similarity to 17-estradiol, and (b) the promotion of insulin-like growth factor-I (IGF-I) production [54,55] (Figure 4). Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. Overall, evidence regarding the use of isoflavones in cancer prevention suggests that they may be useful in reducing the risk of suffering from some types of cancer, such as breast and endometrial cancer, two of the types for which the association between isoflavone intake and cancer risk has been studied more in-depth. In the same line, Yu et al. Furthermore, isoflavones are able to inhibit aromatase activity, the enzyme that converts androgen to estrogen. Regarding endometrial cancer, three prospective and five case-control studies were analyzed, which suggested a lower endometrial cancer risk associated with isoflavone consumption. The unabsorbed isoflavones reach the colon, where they are absorbed after suffering structural modifications by colonic microbiota (Figure 3). They found that the use of dietary isoflavones or supplements and extracts was associated with an improvement in hot flushes, but not with a reduction in the frequency of night sweats. Applegate C.C., Rowles J.L., Ranard K.M., Jeon S., Erdman J.W. Vlachopoulos C., Aznaouridis K., Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: A systematic review and meta-analysis. The moon's gravitational pull affects the water in the soil, which in turn affects the growth of plants. Daidzein, genistein and glycitein occur naturally in the aglycone form, and thus their absorption is faster than that of others. Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells. Collison M.W. The authors indicated that high concentrations of daidzein and genistein (no specific values concerning these concentrations were available) were related to 34% and 28% reduction in breast cancer risk, respectively, whereas no association with equol was found. The moon & # x27 ; s gravitational pull affects the water the. D., Sanders K., Kolybaba M., Lopez D. 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