Study duration ranged from four weeks to two years, with a median of 12 weeks. In fact, in 2015, in relation to the possible adverse effects on the mammary gland, uterus and thyroid, the European Food Safety Agency (EFSA) offered a scientific opinion with regards to the assessment of potential increased risk in peri- and postmenopausal women who took food supplements that contained isolated isoflavones. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. In a study conducted by Karr et al., the authors analyzed the urinary excretion of genistein, daidzein, equol and O-DMA in fourteen young men and women [47]. Lu D., Gigure V. Requirement of Ras-dependent pathways for activation of the transforming growth factor beta3 promoter by estradiol. . Soy isoflavones consumption and risk of breast cancer incidence or recurrence: A meta-analysis of prospective studies. For their meta-analysis, Jiang et al. and transmitted securely. Due to its structural similarity to the estrogen-like compound 17-estradiol (Figure 1), they are referred to as phytoestrogens. In fact, all the body fluids, as the tides, were controlled by the lunar phases. The most significant food source of isoflavones in humans is soy-derived products, soybeans, soy flour, soy flakes, soy beverages and fermented soy products such as miso and tempeh, among others [9]. Non-pharmacological treatments included isoflavones, which appeared to be better than placebo in the relief of vasomotor symptoms, although not significantly better than the treatment with estradiol and progesterone. Nachvak S.M., Moradi S., Anjom-Shoae J., Rahmani J., Nasiri M., Maleki V., Sadeghi O. Soy, Soy Isoflavones, and Protein Intake in Relation to Mortality from All Causes, Cancers, and Cardiovascular Diseases: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies. Regarding endometrial cancer, three prospective and five case-control studies were analyzed, which suggested a lower endometrial cancer risk associated with isoflavone consumption. In some Asian countries, isoflavone intake, usually derived from soy consumption, can be associated with a lower prevalence of cardiovascular diseases (CVDs). In view of the results gathered in the present review, we can conclude that there is scientific evidence that reveals the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis in postmenopausal women. A significant 19% reduction of the risk was found at high concentrations of daidzein, but not at genistein or equol concentrations. This meta-analysis included 266,699 participants (21,612 patients with prostate cancer among them). Abshirini M., Omidian M., Kord-Varkaneh H. Effect of soy protein containing isoflavones on endothelial and vascular function in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. The effect of the moon on planting times is stated as a matter of fact in such popular publications as The Old Farmer's Almanac and books such as Gardening and Planting by the Moon 2018, and, of course, calendars such as The Biodynamic Sowing and Planting Calendar 2018. In addition, genistein and glycitein are transformed into dihydrogenistein and dihydroglycitein, respectively, before being further converted into other metabolites. Their meta-analysis included five studies with a total of 728 menopausal women between 50.5 and 58.5 years old and concluded that women who are not able to produce equol could benefit from equol supplementation. They also indicated that the discrepancies among studies could be due to the duration of the treatment, the type of isoflavone, its dose and the diet. Sfakianos J., Coward L., Kirk M., Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. This fact suggests that other components, such as fiber in the soy foods, may account for these negative associations. 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]. Estradiol, which has proven efficacy on hot flushes, needs 3.09 weeks to achieve half of its peak activity, while isoflavones require 13.4 weeks, suggesting that 12 weeks of treatment is not enough for soy isoflavones to exert a beneficial effect. Future research in this field should quantify isoflavones as accurately as possible, analyzing larger cohorts and lengthening the follow-up stage. (2019) conducted a meta-analysis where 23 prospective studies with a total of 330,826 participants were included. Sirotkin A.V., Harrath A.H. Phytoestrogens and their effects. It is important to point out that the spine has a high proportion of trabecular bone and that this is probably the reason why the spine is thought to be more sensitive to isoflavones. Barnes S. The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. Sansai et al. 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]. Simental-Menda L.E., Gotto A.M., Atkin S.L., Banach M., Pirro M., Sahebkar A. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (, isoflavones, flavonoids, phytoestrogens, soy, bone health, cardiovascular risk, cancer, menopausal symptoms. 2023 Scientific American, a Division of Springer Nature America, Inc. and Rossi et al. Wang X., Dykens J.A., Perez E., Liu R., Yang S., Covey D.F., Simpkins J.W. Lastly, Zhang et al. However, it is important to point out that the beneficial effects of soy isoflavone consumption have been exhibited by women with estrogen receptor-negative breast cancer, but not by women with receptor-positive breast cancer, who present a better prognosis [62]. Most would agree that the daily rising and falling of the moon, along with the monthly waxing and waning cycles, have effects on our oceans and seas. Furthermore, isoflavones are able to inhibit aromatase activity, the enzyme that converts androgen to estrogen. He X., Sun L.M. In conclusion, this study reported some evidence that suggests the beneficial role that daidzein and genistein play in preventing breast cancer risk. Furthermore, isoflavones are associated with proteins; thus, alcohol extraction and processing diminish isoflavone content in foodstuffs such as fermented soybean, tofu or soy beverages. Considering the isoflavone chemical structure, potential health adverse effects of these compounds related to their estrogenic activity have been postulated, despite the scientific opinion offered by EFSA indicating that isoflavone intake was safe. 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. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. An official website of the United States government. 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. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. Gaya P., Medina M., Snchez-Jimnez A., Landete J.M. Moreover, five studies reported side-effect data, and after the analysis, no significant differences were observed between the two groups. Phytoestrogen Metabolism by Adult Human Gut Microbiota. Bethesda, MD 20894, Web Policies In this meta-analysis, 32 randomized controlled trials were analyzed with a sample size of 4165 women over 45 years, with a diagnosis of natural menopause. Bustamante-Rangel M., Delgado-Zamarreo M.M., Perez-Martin L., Rodriguez-Gonzalo E., Dominguez-Alvarez J. 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. Neuroprotective effects of 17beta-estradiol and nonfeminizing estrogens against H. Endoh H., Sasaki H., Maruyama K., Takeyama K., Waga I., Shimizu T., Kato S., Kawashima H. Rapid activation of MAP kinase by estrogen in the bone cell line. Explore our digital archive back to 1845, including articles by more than 150 Nobel Prize winners. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. 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. Continue reading with a Scientific American subscription. The authors declare no conflict of interest. The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism. Nevertheless, this association was not shown when equol or isoflavones were consumed. It is also important to mention that isoflavones could act as potential anticancer compounds due to their antioxidant role in malignant cell proliferation and differentiation (Figure 5). In the end, isoflavones could be useful in reducing hot flushes associated with menopause. Franco O.H., Chowdhury R., Troup J., Voortman T., Kunutsor S., Kavousi M., Oliver-Williams C., Muka T. Use of Plant-Based Therapies and Menopausal Symptoms: A Systematic Review and Meta-analysis. official website and that any information you provide is encrypted (2019) studied whether equol supplementation could benefit equol nonproducer subjects in lowering the incidence and severity of hot flushes [85]. Federal government websites often end in .gov or .mil. 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). Implications of phytoestrogen intake for breast cancer. At high elevations, acidic fog and clouds might . Regarding this topic, three systematic reviews and three meta-analyses were analyzed (Table 2). 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). Finally, isoflavones could be useful in reducing hot flushes associated with menopause. Perna S., Peroni G., Miccono A., Riva A., Morazzoni P., Allegrini P., Preda S., Baldiraghi V., Guido D., Rondanelli M. Multidimensional Effects of Soy Isoflavone by Food or Supplements in Menopause Women: A Systematic Review and Bibliometric Analysis. Liu J., Yuan F., Gao J., Shan B., Ren Y., Wang H., Gao Y. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. Our findings illustrate that foraging rodents, well known to be risk-averse during moonlit nights, are also affected by the presence of an invasive plant. The lunar effect is a purported unproven correlation between specific stages of the roughly 29.5-day lunar cycle and behavior and physiological changes in living beings on Earth, including humans. Abstract BELIEFS that phases of the moon have a differential effect on the rate of development of plants are both ancient and world-wide. Winkel-Shirley B. Biosynthesis of flavonoids and effects of stress. Accessibility Presence of four chemical forms of the three isoflavones found in soybeans. (2020) revised the literature to find randomized controlled trials that evaluated the impact of soy protein supplementation (isoflavone intake ranging from 49.3 to 118 mg/day) on endothelial function parameters in postmenopausal women (n = 802) [58]. (2016) suggested that a daily intake of soy isoflavones, ranging from 20 to 100 mg/day, reduced total cholesterol and triglyceride plasma concentrations, as well as some markers of oxidative stress (nitric oxide and malonaldehyde), thus reducing cardiovascular risk [52]. When a group receiving hormone replacement therapy was included in the study, significant differences between the effects of hormone replacement therapy and soy were found, being the effect of the former superior to that of isoflavones. All authors have read and agreed to the published version of the manuscript. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. After an extensive bibliographical review, the expert panel concluded that the results of observational studies do not support the hypothesis of an increased risk of breast cancer after isoflavone-rich food supplement intake [93]. Santo A.S., Santo A.M., Browne R.W., Burton H., Leddy J.J., Horvath S.M., Horvath P.J. 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. Zhong X.S., Ge J., Chen S.W., Xiong Y.Q., Ma S.J., Chen Q. The effect of soy isoflavones on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials. Soy Consumption and the Risk of Prostate Cancer: An Updated Systematic Review and Meta-Analysis. Effects of isoflavones in different cancer types. As it has been stated in the Bioavailability section, microbiota composition in humans makes equol production very variable, which yields high interindividual differences. He et al. Produced metabolites appear in plasma at variable concentrations and can enter enterohepatic circulation [28]. Furthermore, among the four studies of breast cancer recurrence, three studies found that isoflavone intake decreased the risk of breast cancer recurrence, although further studies are required to confirm this finding [82]. The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. Micek A., Godos J., Brzostek T., Gniadek A., Favari C., Mena P., Libra M., Del Rio D., Galvano F., Grosso G. Dietary phytoestrogens and biomarkers of their intake in relation to cancer survival and recurrence: A comprehensive systematic review with meta-analysis. Is equol production beneficial to health? Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells. Thirty-seven articles presenting evidence of the physiological effects of viewing nature were selected. aimed to compare the effects of animal and plant-sourced proteins on lipemia and blood pressure [60]. Isoflavones are found in several vegetables, mainly in legumes (Fabaceae family) such as soy, white and red clover, alfalfa and beans [9,10]. Juglans regia L. is a traditional plant that has been integrated into traditional medicine since ancient times. In like manner, a meta-analysis by Simental-Menda et al. Reproductive and developmental toxicity studies have stated that 1 g and 2 g of equol per day is safe [96], although further studies are required [92]. Furthermore, soy protein has been linked to an improvement in nitric oxide production and contributes to increased arterial compliance [65]. (2015) concluded that soy isoflavones have both a slight and slow effect in attenuating menopausal hot flushes [87]. Rizzo G., Baroni L. Soy, Soy Foods and Their Role in Vegetarian Diets. 8600 Rockville Pike With regard to isoflavone content in foodstuffs, it has been observed that in soybeans, the amount of these phenolic compounds ranges from 1.2 to 4.2 mg per g on dry weight, whereas in red clover, the amount varies between 10 and 25 mg per g on dry weight [15,16]. (2016) published another systematic review of 23 randomized controlled trials to determine the effect of soy isoflavone extracts on bone mineral density in postmenopausal women [51]. (2020) carried out a meta-analysis with 15 cohort studies with the aim of exploring the association between isoflavone intake (<62.7 mg/day) and breast cancer mortality and its recurrence [68]. It follows that additional high-quality, large-scale randomized controlled trials are needed. Potential health adverse effects in the intake of isoflavones have been postulated due to their estrogenic activity, especially in relation to breast cancer. Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. Despite the positive effect of isoflavones, the authors emphasized that the effects took a long time to appear. For this reason, the bioavailability of isoflavones has been extensively characterized in animal models and humans [25,26,27]. Bhathena S.J., Velasquez M.T. Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: A meta-analysis of prospective cohort studies. Received 2020 Nov 30; Accepted 2020 Dec 15. Possible mechanism of action of isoflavones for menopausal symptoms. Only one study examined the effects of red clover on night sweats, and a significant association was found, which showed a decreased frequency in night sweats. In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. Specifically, the time to achieve half of the efficacy was 11.6 weeks for soy isoflavones, while for the rest of the compounds, the onset time was near 0 weeks. On the contrary, a systematic review and meta-analysis reported by Man et al. Isoflavones (high dose: 0.675.5 mg/day; and low dose: 0.0120.1 mg/day). This chemical feature confers estrogenic or antiestrogenic effects to isoflavones, depending on the cell type and the binding to - or -estrogen receptors. Matulka R.A., Matsuura I., Uesugi T., Ueno T., Burdock G. Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient. Global climate change is not a future problem. Lastly, Abshirini et al. Indeed, some authors speculate that hepatic and lipoprotein lipase activity may have been altered after variable isoflavone intake from soybean, although no experimental data were provided [67]. Scientists not only seek supporting clues, but falsifying clues as well. Thanks for reading Scientific American. They observed that daidzein and genistein intakes were associated with a significant reduction of prostate cancer risk. (2017) included 26 trials with 2652 participants [48]. Applegate C.C., Rowles J.L., Ranard K.M., Jeon S., Erdman J.W. The authors reported that neither soy food intake nor circulating isoflavones were associated with a reduced risk of prostate cancer. (2016), nine studies addressed to menopausal women and focused on bone health were analyzed [52]. (2016) reviewed seven studies and concluded that the evidence supports the fact that isoflavones, at a dose of 5020 mg/day, decrease the frequency of hot flushes [52]. 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. (2018) performed a meta-analysis of 12 studies, where six were cohort studies, and six case-control studies, with a total of 596,553 participants [81]. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. ); sue.uhe@ollitrop.yupairam (M.P.P. With regard to the mechanisms by which isoflavones act to reduce cancer risk, it has been suggested that the effects are due to the similarity of the isoflavone molecule to estradiol. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering from some types of cancer, such as breast and endometrial cancer, although further studies are needed to confirm these results. However, the authors pointed out several limitations of this study, such as the important source of heterogeneity in their study. However, the results do not seem entirely conclusive, for there are discrepancies among the studies, probably related to their experimental designs. The six meta-analyses show a slight improvement in the frequency and intensity of hot flushes. From laboratory experiments, it's known that light intensities as low as 0.1 lux (approximately 0.01 foot-candle) during the night can influence photoperiodic time measurement in some plants and animals. Regarding the mechanisms by which isoflavones act to alleviate vasomotor symptoms, is has been proposed that they bind to estrogen receptors and activate endothelial nitric oxide synthase (eNOS) transcription, leading to eNOS synthesis and nitric oxide production, the main mediator of vasodilatation, which allows cutaneous heat dissipation [91] (Figure 6). Acid rain also removes minerals and nutrients from the soil that trees need to grow. Regarding this topic, three prospective and five case-control studies, probably related to their experimental designs slight slow. Addressed to menopausal women and focused on bone health were analyzed [ 52 ] ]..., Dong L., Kirk M., Snchez-Jimnez A., Landete J.M isoflavones for menopausal.. Simental-Menda L.E., Gotto A.M., Atkin S.L., Banach M., A.. Pathways for activation of the moon have a differential effect on the ERalpha-agonist induced proliferation of human T47D cancer. 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