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]. After the consumption of around 17 mg of isoflavones per day, the median plasma concentrations of genistein, glycitein, daidzein and equol were 245.3 ng/mL, 9.8 ng/mL, 86.8 ng/mL and 12.7 ng/mL, respectively. It follows that additional high-quality, large-scale randomized controlled trials are needed. In addition, genistein and glycitein are transformed into dihydrogenistein and dihydroglycitein, respectively, before being further converted into other metabolites. Interestingly, in a study conducted by Tamura et al., the authors observed that in individuals without the LPH enzyme, the concentration of isoflavones and derived metabolites was similar to that found in individuals without an enzyme deficiency. Further, Chalvon-Demersay et al. (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]. Comparative efficacy of nonhormonal drugs on menopausal hot flashes. "It's not. Juglans regia L. is a traditional plant that has been integrated into traditional medicine since ancient times. Another meta-analysis explored the effects of several pharmacological and non-pharmacological treatments in the relief of vasomotor symptoms, taking into account not only hot flushes but also night sweats [89]. Morning 3: Temp 98.6 BP 124/83 Pulse 62 bpm. 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]. Daily et al. In addition, several studies have observed that the urine excretion of daidzein metabolites is notably higher than that of genistein metabolites [44,45,46]. Due to the high prevalence of colorectal cancer, three meta-analyses addressing this issue are included in the present review. Reduction of the endometrial thickness in North American women (for 0.23 mm). This fact suggests that other components, such as fiber in the soy foods, may account for these negative associations. Postprandial lipemia detects the effect of soy protein on cardiovascular disease risk compared with the fasting lipid profile. As far as the mechanisms of action involved in the decrease in triglyceride concentration are concerned, it has been reported that hepatic lipase and/or lipoprotein lipase activity may be increased as a result of isoflavone presence. Implications of phytoestrogen intake for breast cancer. Thus, its consumption, according to epidemiological and clinical studies, has been postulated to be related to a decrease in the risk of different diseases. (2017) conducted a meta-analysis with ten observational studies to assess the association between the isoflavone compounds daidzein, genistein and equol, and breast cancer [61]. The authors observed that soy isoflavone consumption was inversely associated with cancer deaths. The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. ; WritingOriginal Draft Preparation, S.G.-Z., M.G.-A., A.F.-Q., I.E. It is well-known that some of the most accurate BP readings occur right as someone wakes up and at that event, the BP will be shown for the most part to stay lower than that of a daily average. and J.T. 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. Abstract BELIEFS that phases of the moon have a differential effect on the rate of development of plants are both ancient and world-wide. 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]. In the end, isoflavones could be useful in reducing hot flushes associated with menopause. Changes to Earth's climate driven by increased human emissions of heat-trapping greenhouse gases are already having widespread effects on the environment: glaciers and ice sheets are shrinking, river and lake ice is breaking up earlier, plant and animal geographic ranges are shifting, and plants and trees are blooming sooner. Bethesda, MD 20894, Web Policies Metabolism of intraruminally administered [4-. (2018) showed no effect of soy isoflavones on plasma concentrations of lipoprotein a (Lpa), a low-density lipoprotein associated with increased cardiovascular risk due to its pro-thrombotic and atherogenic properties [63]. In this sense, Micek et al. Thanks for reading Scientific American. (2017) included 26 trials with 2652 participants [48]. Cheynier V., Sarni-Manchado P., Quideau S., editors. Jun S., Shin S., Joung H. Estimation of dietary flavonoid intake and major food sources of Korean adults. There are a total of 15 3 = 3375 possible outcomes. However, the authors pointed out several limitations of this study, such as the important source of heterogeneity in their study. Isoflavones (high dose: 0.675.5 mg/day; and low dose: 0.0120.1 mg/day). That's what behavioral ecologist Jenny York learned while studying white-browed sparrow weavers . Dong J.Y., Qin L.Q. However, more studies are required to provide stronger evidence. 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. 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. Batterham T.J., Shutt D.A., Braden A.W.H., Tweeddale H.J. The unabsorbed isoflavones reach the colon, where they are absorbed after suffering structural modifications by colonic microbiota (Figure 3). 8600 Rockville Pike A total of 16 studies were included in their meta-analysis with a range of 24 to 236 subjects. 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. The moon's gravitational pull affects the water in the soil, which in turn affects the growth of plants. 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. government site. However, all the authors agree that further studies are necessary so as to confirm these results. http://creativecommons.org/licenses/by/4.0/, https://data.nal.usda.gov/dataset/usda-database-isoflavone-content-selected-foods-release-20, Acetyldaidzin, acetylgenistin, acetylglycitin, Malonyldaidzin, malonylgenistin, malonylglycitin, Moderate attenuation of bone loss, primarily at the level of the lumbar spine and the femoral neck, Prevention of osteoporosis-related bone loss in any weight status or treatment duration, Isoflavone interventions, genistein (54 mg/day) and ipriflavone (600 mg/day) in particular hold great promise in the prevention and treatment of bone mineral density, Probably they have beneficial effects on bone health in menopausal women but there are controversial reports about changes in bone mineral density, Soy isoflavones (2080 mg) and equol (10 mg), 1Meta-analysis 1Systematic review and 1clinical trial, Attenuation of lumbar spine bone mineral density, Prospective cohort and case-control studies, 508,841 participants, 17,269 with CVD events (stroke, coronary heart disease, ischemic stroke), No associations between soy isoflavones consumption and risk of cardiovascular disease, stroke, and coronary heart disease, 548 participants (272 case and 276 controls), Non-significant change in flow-mediated dilation (parameter of endothelial function), Various designs (double-blind, placebo-controlled, parallel design, crossover design), Isoflavones 80118 mg/day and 10 mg/day of S-equol, Positive effect of soy isoflavones on arterial stiffness, 1391268 menopausal and postmenopausal women, Reduction in total cholesterol and triglyceride plasma concentrations, 337 healthy, diabetic or hypercholesterolemic individuals, Reduction in total cholesterol and LDL cholesterol, Decreased risk of acute coronary syndrome or coronary heart disease, 9% lower risk of estrogen receptor-negative breast cancer mortality, Inverse association between isoflavone intake and both overall mortality and breast cancer recurrence, Isoflavones (the amount varies greatly among different soy foods), Pre-diagnosis, soy isoflavone consumption has a poor effect on survival of postmenopausal women, High dietary intake of soy foods (dose non-defined), Significant reduction of breast cancer risk, Sample sizes (from 100 to 15,688 participants), Daidzein, genistein, and equol (dose non-defined), Daidzein (34%) and genistein (28%) were associated with a lower risk of breast cancer, Prospective cohort study (3) Case-control study (10), 178,947 (7067 cases and 171,880 controls). 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. Kov L., Dadkov K., Kaparovsk J., Kaparovsk T. Isoflavones. Winkel-Shirley B. Biosynthesis of flavonoids and effects of stress. In their systematic revision, which included 1307 menopausal (n = 139) and post-menopausal (n = 1268) women, Perna et al. 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. The work reported by Lambert et al. Furthermore, isoflavones are able to inhibit aromatase activity, the enzyme that converts androgen to estrogen. Whilst soy isoflavones show positive effects when compared with placebo, synthetic, or a combination of different types of isoflavones seem to be more effective than natural soy. However, some limitations were found in these prospective studies, such as the small sample size of the cohorts and the unspecific definition of high, moderate and low isoflavone intake. 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. An official website of the United States government. This result has implications for granivory and perhaps plant demography in invaded and restored coastal habitats. Ronis M.J., Little J.M., Barone G.W., Chen G., Radominska-Pandya A., Badger T.M. In the systematic review reported by Perna et al. 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]. So long ago as 1880 Siemens showed that continuous exposure to arc lamps promoted luxuriance of foliage . Hairi H.A., Shuid A.N., Ibrahim N., Jamal J.A., Mohamed N., Mohamed I.N. Equol has been considered as the most interesting colonic metabolite due to its beneficial biological activity, which differs from that of its precursor, daidzein [13,38,39]. Interestingly, soy protein isolate (void of isoflavones through alcoholic extraction during the protein solation phase) did not show these effects. 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. In some Asian countries, isoflavone intake, usually derived from soy consumption, can be associated with a lower prevalence of cardiovascular diseases (CVDs). In any case, it is important to bear in mind that a great number of expert scientists and doctors think that breast cancer survivors should not increase their isoflavone intake [94], although others consider that their consumption is safe and beneficial [95]. In general terms, it has been observed that in Asian countries where there is high consumption of soy and its derived foodstuffs, isoflavone intake is high, ranging from 15 to 60 mg/day [20,21], whereas, in western countries, it is notably lower, around 12 mg/day [22,23,24]. (2019) studied whether equol supplementation could benefit equol nonproducer subjects in lowering the incidence and severity of hot flushes [85]. 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. Zhong et al. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. It has been described that after the oral intake of isoflavones, their peak plasma concentration in humans occurs at around seven hours [33]. In fact, all the body fluids, as the tides, were controlled by the lunar phases. Indeed, the dose levels of dietary isoflavones require a better definition, and the measurements of isoflavone consumption should be provided in quantifiable terms. Sansai K., Na Takuathung M., Khatsri R., Teekachunhatean S., Hanprasertpong N., Koonrungsesomboon N. Effects of isoflavone interventions on bone mineral density in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. Karr S.C., Lampe J.W., Hutchins A.M., Slavin J.L. The latter is the most common form in foodstuffs, with the exception of fermented soy products, such as miso and tempeh. 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]. Prez-Cornago et al. However, the moonlight decreases after the full moon. 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]. 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. THE effect of light on plant life has been the subject of many scientific investigations. Create your free account or Sign in to continue. In: Thompson M.J., editor. (2015), the authors examined the efficacy of phytoestrogens in reducing hot flushes [86]. In this section, 16 meta-analyses have been revised: Nachvack et al. This finding suggests that bacterial deglycosylation contributes significantly to isoflavone absorption [32]. The physical stiffening of arteries has major health implications for its connection to various adverse cardiovascular and other health outcomes such as coronary heart disease, stroke, hypertension or heart failure [66]. 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. Possible mechanism of action of isoflavones for menopausal symptoms. Although smaller in quantity, isoflavones are also present in chickpeas, nuts, fruits and vegetables [11]. However, the results do not seem entirely conclusive, for there are discrepancies among the studies, probably related to their experimental designs. The intensity of moonlight at different times during the month can also affect the development of plants. Possible mechanism of action of isoflavones for cancer prevention. Global climate change is not a future problem. The increased moonlight enhances leaf growth during the new moon and second quarter. Federal government websites often end in .gov or .mil. 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. 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. Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells. Even though red clover has a greater amount of isoflavones, it is not an edible plant, and it is consumed as a food complement. Effects of Acid Rain on Plants and Trees. In Japanese men, pre-diagnostic circulating levels of genistein, daidzein and equol did not significantly affect prostate cancer risk. Licensee MDPI, Basel, Switzerland. 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]. Is equol production beneficial to health? Kurzer M.S., Xu X. Dietary phytoestrogens. Yan Z., Zhang X., Li C., Jiao S., Dong W. Association between consumption of soy and risk of cardiovascular disease: A meta-analysis of observational studies. Duffy C., Perez K., Partridge A. 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. 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. Perna et al. Metabolites of dietary (soya) isoflavones in human urine. ; Funding Acquisition, M.P.P. They discuss their differences and resolve the discrepancies, if possible. Sex and long-term soy diets affect the metabolism and excretion of soy isoflavones in humans. [12,42]. 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 Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism. (2016), nine studies addressed to menopausal women and focused on bone health were analyzed [52]. 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. Moreover, Rienks et al. Effect of soy isoflavone supplementation on plasma lipoprotein(a) concentrations: A meta-analysis. 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. As it has been stated in the Bioavailability section, microbiota composition in humans makes equol production very variable, which yields high interindividual differences. The results showed that a higher regular intake of foods rich in isoflavones might potentially decrease colorectal cancer incidence. In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. Chen L.R., Ko N.Y., Chen K.H. Most peculiar is that moonlight exposure causes a rise in blood pressure. (2017) conducted a meta-analysis with 21 case-control studies and two cohort studies, with a total number of 11,346 cases and 140,177 controls [77]. Association between Dietary Isoflavones in Soy and Legumes and Endometrial Cancer: A Systematic Review and Meta-Analysis. In view of these results, we can conclude that there is scientific evidence that supports the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis in postmenopausal women. Before Isoflavone excretion occurs mainly through urine and feces, primarily in the conjugate forms, and up to 95% takes place in 24 h [43]. You et al. 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. Isoflavone content in soy-derived products is usually lower than in soybeans [17]. U.S. Department of Agriculture Database for the Isoflavone Content of Selected Foods, Release 2.0. 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