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. ; WritingOriginal Draft Preparation, S.G.-Z., M.G.-A., A.F.-Q., I.E. Continue reading with a Scientific American subscription. Phytoestrogen Metabolism by Adult Human Gut Microbiota. Metabolism of intraruminally administered [4-. Kim Y., Je Y. Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. Therefore, it is necessary to support these results with additional studies. 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. Potential health adverse effects in the intake of isoflavones have been postulated due to their estrogenic activity, especially in relation to breast cancer. (2016) conducted a meta-analysis aimed at ovarian cancer, which affects women exclusively [74]. There are a total of 15 3 = 3375 possible outcomes. Grosso et al. Grosso G., Godos J., Lamuela-Raventos R., Ray S., Micek A., Pajak A., Sciacca S., DOrazio N., Del Rio D., Galvano F. A comprehensive meta-analysis on dietary flavonoid and lignan intake and cancer risk: Level of evidence and limitations. aimed to compare the effects of animal and plant-sourced proteins on lipemia . 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]. Lastly, Abshirini 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. As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. 2023 Scientific American, a Division of Springer Nature America, Inc. Moonlight sonata. The light of the moon also influences animals that are active in daytime. Effects of Acid Rain on Plants and Trees. In contrast, the effects on bone resorption biomarkers were more favorable in overweight or obese women than in women with a healthy weight. Gut bacterial metabolism of the soy isoflavone daidzein: Exploring the relevance to human health. 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. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. (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]. 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. This fact was not taken into account in previous meta-analyses, and thus it may justify the discrepancies amongst them. 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. and Rossi et al. Additionally, Yan and co-workers, in their meta-analysis with a total of ten prospective cohorts and seven case-control studies (including 508,841 participants and 17,269 cardiovascular disease events), observed that the consumption of soy foods, but not that of isoflavones, was associated with a lower risk of total cardiovascular disease (including coronary heart disease and stroke) [57]. Soy isoflavones and their metabolites modulate cytokine-induced natural killer cell function. Knowledge awaits. Received 2020 Nov 30; Accepted 2020 Dec 15. Jun S., Shin S., Joung H. Estimation of dietary flavonoid intake and major food sources of Korean adults. Endometrial cancer (Table 4), as well as breast cancer, is an estrogen-dependent cancer type related to high circulating estradiol concentrations. The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. In this sense, soy isoflavones have been proposed as beneficial because, in theory, they may contribute to the maintenance of good bone health (mass, mineral density and bone structure) in women who are at this stage in their life. 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. This difference could explain the slow effect of isoflavones in alleviating hot flushes. 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). The authors observed that soy isoflavone consumption was inversely associated with cancer deaths. 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]. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. However, the authors pointed out several limitations of this study, such as the important source of heterogeneity in their study. Winkel-Shirley B. Biosynthesis of flavonoids and effects of stress. In the same line, Yu et al. (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]. 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). Sfakianos J., Coward L., Kirk M., Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. (2020) revealed that supplementation of soy isoflavones had a positive effect in reducing arterial stiffness, also known as the loss of arterial elasticity [59]. Cheynier V., Sarni-Manchado P., Quideau S., editors. The .gov means its official. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. Moreover, an increase in thyroid hormone levels after isoflavone intake by food supplements has not been observed, and no side effects were confirmed with regard to the endometrial thickness or histopathological changes in the uterus. Bethesda, MD 20894, Web Policies They discuss their differences and resolve the discrepancies, if possible. Regarding the effect of specific isoflavones, they suggested that genistein, alone or in combination with daidzein, improved bone density and bone turnover in women after menopause. Proof by rational experiment seems to have been. 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. Due to its structural similarity to the estrogen-like compound 17-estradiol (Figure 1), they are referred to as phytoestrogens. Prez-Cornago et al. 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. They observed that it was dose-dependent at low to moderate soybean consumption. The aglycone and conjugate forms of genistein represent up to 60% of total isoflavones, this being up to 30% in the case of daidzein. With regard to the published meta-analysis, the studies included were restricted to randomized controlled trials. 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]. But that doesn't mean that they dig in their heels and argue about it. Daily et al. Hosoda K., Furuta T., Yokokawa A., Ishii K. Identification and quantification of daidzein-7-glucuronide-4-sulfate, genistein-7-glucuronide-4-sulfate and genistein-4,7-diglucuronide as major metabolites in human plasma after administration of kinako. Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract. In a more recent systematic review, including two meta-analyses, as well as one multicenter and randomized controlled trial, Chen and his team concluded that isoflavones reduced lumbar spine bone mineral density loss [53]. Implications of phytoestrogen intake for breast cancer. 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. Isoflavone intake in four different European countries: The VENUS approach. Man B., Cui C., Zhang X., Sugiyama D., Barinas-Mitchell E., Sekikawa A. Isoflavone content in soy-derived products is usually lower than in soybeans [17]. Isoflavones were the phytoestrogens used in most of the studies; therefore, the meta-analysis only included outcomes regarding isoflavones, while outcomes with other phytoestrogens were not included. National Library of Medicine In like manner, a meta-analysis by Simental-Menda et al. Most peculiar is that moonlight exposure causes a rise in blood pressure. (2019) studied whether equol supplementation could benefit equol nonproducer subjects in lowering the incidence and severity of hot flushes [85]. The improvement was greater in treatments lasting more than one year and in subjects with normal weight, probably because subjects with excessive body weight have a lesser risk of bone loss. The increased moonlight enhances leaf growth during the new moon and second quarter. In a study reported by Ko et al., the authors quantified the plasma concentrations of daidzein, genistein, glycitein and equol in Korean men and women [36]. Bacterial metabolites of isoflavones forming in the gut. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. Postprandial lipemia detects the effect of soy protein on cardiovascular disease risk compared with the fasting lipid profile. Lund S., Holman G.D., Schmitz O., Pedersen O. Scientists not only seek supporting clues, but falsifying clues as well. Discover world-changing science. Isoflavones (high dose: 0.675.5 mg/day; and low dose: 0.0120.1 mg/day). (2017) also analyzed eight studies of prostate cancer, and they found an association between isoflavone intake and prostate cancer risk [61]. (2015) concluded that soy isoflavones have both a slight and slow effect in attenuating menopausal hot flushes [87]. (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]. Possible mechanism of action of isoflavones for cancer prevention. (2018) analyzed 12 studies with 37,275 women with breast cancer and reported that soy isoflavone consumption at a pre-diagnosis stage might have a small effect on the survival of postmenopausal women with breast cancer [69]. Association of isoflavone biomarkers with risk of chronic disease and mortality: A systematic review and meta-analysis of observational studies. The most significant food source of isoflavones in humans is soy-derived products. In this revision, three systematic reviews and five meta-analyses were included to explore the association of isoflavones and markers related to CVDs (Table 3). Treutter D. Significance of flavonoids in plant resistance and enhancement of their biosynthesis. (2015), the authors examined the efficacy of phytoestrogens in reducing hot flushes [86]. 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. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. This finding suggests that bacterial deglycosylation contributes significantly to isoflavone absorption [32]. (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]. The two systematic reviews conclude that isoflavones have an important role in reducing hot flushes [52,53], although some observations need to be pointed out. However, more studies are required to provide stronger evidence. Despite the positive effect of isoflavones, the authors emphasized that the effects took a long time to appear. government site. 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. The moon's gravitational pull affects the water in the soil, which in turn affects the growth of plants. (2019) conducted a meta-analysis where 23 prospective studies with a total of 330,826 participants were included. Before Taken as a whole, all these results suggest that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Moreover, five studies reported side-effect data, and after the analysis, no significant differences were observed between the two groups. To address the link between lunar phases and agriculture from a scientic perspective, we conducted a review of textbooks and monographs used to teach agronomy, botany, horticulture and plant physiology; we also consider the physics that address the e ects of the Moon on our planet. Similarly, Li et al. However, the magnitude of risk reduction in Asian women was slightly larger than in non-Asian women (22% vs. 18%). (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]. (At least not real scientists.) In addition, it is important to highlight that interindividual differences in gut bacterial populations are responsible for the diverse effects of isoflavones in humans. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. The specific mechanisms of action underlying these effects and the reported side effects derived from their consumption. 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]. The six meta-analyses show a slight improvement in the frequency and intensity of hot flushes. . Possible mechanism of action of isoflavones for menopausal symptoms. 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. Thirty-nine studies were included with a sample size of 200 women per trial, in which the intervention period ranged from two to 96 weeks (median 12 weeks). Rienks et al. Abdi F., Alimoradi Z., Haqi P., Mahdizad F. Effects of phytoestrogens on bone mineral density during the menopause transition: A systematic review of randomized, controlled trials. Lambert M.N.T., Hu L.M., Jeppesen P.B. Moreover, Rienks et al. Isoflavone Supplements for Menopausal Women: A Systematic Review. Of insulin the frequency and intensity of hot flushes [ 87 ] and! A healthy weight paid a protective role against ovarian cancer, which scientific evidence regarding the effects of moonlight on plants women [. Of Medicine in like manner, a Division of Springer Nature America, Inc. moonlight.... 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