After this, each metabolite undergoes its own metabolic pathway [40]. Watanabe S., Yamaguchi M., Sobue T., Takahashi T., Miura T., Arai Y., Mazur W., Whl K., Adlercreutz H. Pharmacokinetics of soybean isoflavones in plasma, urine and feces of men after ingestion of 60 g baked soybean powder (kinako). 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. The main forms of conjugates in soybeans are the malonyl derivatives [14]. However, the authors stated that they could not reach definitive conclusions due to, among other reasons, the lack of inclusion in the review of randomized controlled clinical trials focused on the treatment of osteoporosis in early menopause. In addition, several studies have observed that the urine excretion of daidzein metabolites is notably higher than that of genistein metabolites [44,45,46]. Dietary intake of flavonoid subclasses and risk of colorectal cancer: Evidence from population studies. Zamora-Ros R., Knaze V., Rothwell J.A., Hmon B., Moskal A., Overvad K., Tjnneland A., Kyr C., Fagherazzi G., Boutron-Ruault M.C., et al. Valsta L.M., Kilkkinen A., Mazur W., Nurmi T., Lampi A.M., Ovaskainen M.L., Korhonen T., Adlercreutz H., Pietinen P. Phyto-oestrogen database of foods and average intake in Finland. Finally, it is important to mention that despite the fact that potential isoflavone adverse effects have been widely studied, little is known about the side effect of the bacterial metabolite equol. Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells. All authors have read and agreed to the published version of the manuscript. In the aforementioned mechanism, it has been reported that isoflavones bind to both ER and ER, although they present a higher affinity towards ER receptors [7]. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. Chemical structure of 17-estradiol. THE effect of light on plant life has been the subject of many scientific investigations. In the last few decades, scientific evidence has stressed the importance of plants in the prevention and/or supportive treatment of a plethora of diseases, many of them chronic, age-associated disorders. Duffy C., Perez K., Partridge A. Regarding blood pressure, inconsistent results were reported in three further interventional studies (n = 406 healthy, postmenopausal or obese participants aged 5079 years) either in diastolic or systolic blood pressure, after a supplementation with soy-protein. Bethesda, MD 20894, Web Policies By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Science is Knowledge Space & Physics The Effects of Moonlight May 22, 1858 Professor Piazza Smyth, the Astronomer Royal for Scotland, in his interesting account of a recent scientific. Concerning this issue, six meta-analyses and two systematic reviews are included in the present review (Table 5). The enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. 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. Many females sleep less and have less REM sleep. This meta-analysis included 266,699 participants (21,612 patients with prostate cancer among them). Saloniemi H., Whl K., Nyknen-Kurki P., Kallela K., Saastamoinen I. Phytoestrogen content and estrogenic effect of legume fodder. Modified from Mace et al. The authors declare no conflict of interest. (2018) published a meta-analysis of seven prospective cohort studies (two studies from Japan with 241 cases and 503 controls, and five studies from Europe with 2828 cases and 5593 controls) [75]. 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. You J., Sun Y., Bo Y., Zhu Y., Duan D., Cui H., Lu Q. (2015) concluded that soy isoflavones have both a slight and slow effect in attenuating menopausal hot flushes [87]. A significant 19% reduction of the risk was found at high concentrations of daidzein, but not at genistein or equol concentrations. 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. Endometrial cancer (Table 4), as well as breast cancer, is an estrogen-dependent cancer type related to high circulating estradiol concentrations. Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: A meta-analysis of prospective cohort studies. Li L., Lv Y., Xu L., Zheng Q. Quantitative efficacy of soy isoflavones on menopausal hot flashes. (2016) analyzed the effect of oral isoflavone supplementation on endometrial thickness in pre- and post-menopausal women, which is a biomarker for the proliferative effects of estrogens associated with an increased endometrial risk [72]. Furthermore, isoflavones are associated with proteins; thus, alcohol extraction and processing diminish isoflavone content in foodstuffs such as fermented soybean, tofu or soy beverages. Atkinson C., Frankenfeld C.L., Lampe J.W. (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]. (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]. In the meta-analysis reported by Applegate et al. Cheynier V., Sarni-Manchado P., Quideau S., editors. Perez-Cornago A., Appleby P.N., Boeing H., Gil L., Kyr C., Ricceri F., Murphy N., Trichopoulou A., Tsilidis K.K., Khaw K.T., et al. ); sue.uhe@zednanref.oderfla (A.F.-Q. 19% reduction in endometrial cancer risk. Furthermore, isoflavones are able to inhibit aromatase activity, the enzyme that converts androgen to estrogen. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. The site is secure. . The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. Determination of total soy isoflavones in dietary supplements, supplement ingredients, and soy foods by high-performance liquid chromatography with ultraviolet detection: Collaborative study. Zhao T.T., Jin F., Li J.G., Xu Y.Y., Dong H.T., Liu Q., Xing P., Zhu G.L., Xu H., Miao Z.F. However, a limitation in this field is that there is still a great heterogeneity among studies. The meta-analysis included 15 studies in which the number of participants ranged from 30 to 252. Moreover, this association was more prominent among postmenopausal women than premenopausal women. He Bays that his thermometrical instruments were sensibly affected by the moon's rays, even at the lowest of two stations occupied by him at different elevations. So long ago as 1880 Siemens showed that continuous exposure to arc lamps promoted luxuriance of foliage . In: Thompson M.J., editor. In Japanese men, pre-diagnostic circulating levels of genistein, daidzein and equol did not significantly affect prostate cancer risk. Further, Chalvon-Demersay et al. Phenolic compounds, characterized by the presence of a hydroxyl group attached to at least one aromatic ring, can be classified as flavonoids and non-flavonoids. Gut bacterial metabolism of the soy isoflavone daidzein: Exploring the relevance to human health. 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. Kurzer M.S., Xu X. Dietary phytoestrogens. Analysis of isoflavones in Foods. Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. (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]. On the contrary, a systematic review and meta-analysis reported by Man et al. It has been described that after the oral intake of isoflavones, their peak plasma concentration in humans occurs at around seven hours [33]. 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. This result has implications for granivory and perhaps plant demography in invaded and restored coastal habitats. HRT: hormone replacement therapy, RCT: randomized controlled trial, VSM: vasomotor symptoms. Isoflavones are found in several vegetables, mainly in legumes (Fabaceae family) such as soy, white and red clover, alfalfa and beans [9,10]. Effects of Acid Rain on Plants and Trees. Implications of phytoestrogen intake for breast cancer. It supports the evidence that isoflavones can moderately attenuate bone resorption in women with low estrogen levels, primarily at the level of the lumbar spine and the femoral neck. Another meta-analysis, conducted by Zhao et al. 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. Scientists often disagree about certain things. Kim Y., Je Y. Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. ; WritingOriginal Draft Preparation, S.G.-Z., M.G.-A., A.F.-Q., I.E. Sarri G., Pedder H., Dias S., Guo Y., Lumsden M.A. This is mainly due to their potential adverse effects, which range from increased coronary heart disease to stroke and cancer [53,85]. Isoflavone Supplements for Menopausal Women: A Systematic Review. Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway. 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. Menopause is characterized by a decrease in estrogen levels and is often accompanied by a range of symptoms. Indeed, the dose levels of dietary isoflavones require a better definition, and the measurements of isoflavone consumption should be provided in quantifiable terms. 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 majority of the studies that used display stimuli, such as photos, 3D images, virtual reality, and videos of natural landscapes, confirmed that viewing natural scenery led to more relaxed body responses than viewing the control. (2018), 30 articles were included for analysis; 15 of them were case-control studies, eight cohort studies and seven nested case-control studies [76]. 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. Nevertheless, the metabolism of formononetin and biochanin A, the main isoflavones in red clover, has been less studied due to their limited presence in foodstuffs. In some cases the purported effect may depend on external cues, such as the amount of moonlight. The water in the ocean on the side of the Earth closest to the moon experiences a larger gravitational attraction than the water on the opposite side. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Produced metabolites appear in plasma at variable concentrations and can enter enterohepatic circulation [28]. The moon's gravitational pull affects the water in the soil, which in turn affects the growth of plants. Chen L.R., Ko N.Y., Chen K.H. Vlachopoulos C., Aznaouridis K., Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: A systematic review and meta-analysis. 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. But that doesn't mean that they dig in their heels and argue about it. The same results were reported in another meta-analysis published by the same authors a year later (Li et al., 2016), when they compared the efficacy of several non-hormonal drugs on hot flushes, including selective serotonin reuptake inhibitors (SSRIs), serotoninnorepinephrine reuptake inhibitors (SNRIs), gabapentin, clonidine and soy isoflavones [88]. Isoflavone glycosides have to be hydrolyzed to the aglycone form prior to its absorption by passive diffusion in the upper small intestine [28]. The effect of soy isoflavones on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials. Although smaller in quantity, isoflavones are also present in chickpeas, nuts, fruits and vegetables [11]. In their systematic revision, which included 1307 menopausal (n = 139) and post-menopausal (n = 1268) women, Perna et al. 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]. Bacterial metabolites of isoflavones forming in the gut. and Rossi et al. Metabolites of dietary (soya) isoflavones in human urine. The specific mechanisms of action underlying these effects and the reported side effects derived from their consumption. Soy isoflavones and their metabolites modulate cytokine-induced natural killer cell function. and A.F.-Q. Zhong et al. Despite the positive effect of isoflavones, the authors emphasized that the effects took a long time to appear. Some authors label equol as an isoflavone; however, since it is a daidzein-derived bacterial metabolite and not a naturally occurring isoflavone, this classification is not correct [10]. ; Project Administration, M.P.P. . Lund S., Holman G.D., Schmitz O., Pedersen O. The main isoflavones found in foodstuffs are daidzein, genistein and glycitein, as well as biochanin A and formononetin [9,12]. The latter is the most common form in foodstuffs, with the exception of fermented soy products, such as miso and tempeh. sharing sensitive information, make sure youre on a federal (2017) included 26 trials with 2652 participants [48]. These positive effects were associated with 54 mg/day of genistein and 600 mg/day of synthetic isoflavone ipriflavone. 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. Kov L., Dadkov K., Kaparovsk J., Kaparovsk T. Isoflavones. He et al. As previously mentioned, soybeans and their derived foodstuffs are the main isoflavone sources in the human diet, at least if we do not consider red clover extract supplements, which are being widely used by menopausal women as nutraceutical therapy [13]. This study was supported by Instituto de Salud Carlos III (CIBERobn) under Grant CB12/03/30007, Basque Government under Grant PA20/04 and the University of the Basque Country under Grant GIU18-173. 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). Grosso et al. With regard to the published meta-analysis, the studies included were restricted to randomized controlled trials. However, the intake of specific isoflavones, genistein and daidzein, was indeed significantly associated with a reduced risk of this type of cancer. Acid rain leaches aluminum from the soil. The results showed that a higher regular intake of foods rich in isoflavones might potentially decrease colorectal cancer incidence. 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. Potential health adverse effects in the intake of isoflavones have been postulated due to their estrogenic activity, especially in relation to breast cancer. Chadha R., Bhalla Y., Jain A., Chadha K., Karan M. Dietary Soy Isoflavone: A Mechanistic Insight. In addition, it is important to highlight that interindividual differences in gut bacterial populations are responsible for the diverse effects of isoflavones in humans. Jun S., Shin S., Joung H. Estimation of dietary flavonoid intake and major food sources of Korean adults. Perna et al. Yu Y., Jing X., Li H., Zhao X., Wang D. Soy isoflavone consumption and colorectal cancer risk: A systematic review and meta-analysis. The authors indicated that no consensus was found regarding the protective effects of soy isoflavones (2080 mg) and equol (10 mg) on bone resorption. Thus, soybean can be considered as the best food source. Arjmandi B.H., Smith B.J. 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. Batterham T.J., Shutt D.A., Braden A.W.H., Tweeddale H.J. Beneficial role of dietary phytoestrogens in obesity and diabetes. Lastly, the association between dietary isoflavone intake and the risk of developing gastric cancer has also been analyzed. In contrast, the effects on bone resorption biomarkers were more favorable in overweight or obese women than in women with a healthy weight. Tamura A., Shiomi T., Hachiya S., Shigematsu N., Hara H. Low activities of intestinal lactase suppress the early phase absorption of soy isoflavones in Japanese adults. Soy isoflavones osteoprotective role in postmenopausal women: Mechanism of action. Two of the studies also revealed that women who were able to produce equol or who had received equol supplementation could have had a greater benefit from isoflavones [53]. 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. (2016) conducted a meta-analysis of 18 studies involving 16,917 colorectal cancer cases in 559,486 participants [78]. The aglycone and conjugate forms of genistein represent up to 60% of total isoflavones, this being up to 30% in the case of daidzein. Licensee MDPI, Basel, Switzerland. (2016) conducted a meta-analysis aimed at ovarian cancer, which affects women exclusively [74]. 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