Explore our digital archive back to 1845, including articles by more than 150 Nobel Prize winners. 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]. Rossi M., Amaretti A., Roncaglia R., Leonardi A., Raimondi S. Dietary isoflavones and dietary microbiota: Metabolism and transformation into bioactive compounds. There are a total of 15 3 = 3375 possible outcomes. (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]. Scientists often disagree about certain things. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. Due to a decline in sunlight, the development of leaves . In the meta-analysis reported by Chen et al. Presence of four chemical forms of the three isoflavones found in soybeans. Chadha R., Bhalla Y., Jain A., Chadha K., Karan M. Dietary Soy Isoflavone: A Mechanistic Insight. Even though red clover has a greater amount of isoflavones, it is not an edible plant, and it is consumed as a food complement. Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. Is equol production beneficial to health? Daily J.W., Ko B.S., Ryuk J., Liu M., Zhang W., Park S. Equol Decreases Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Produced metabolites appear in plasma at variable concentrations and can enter enterohepatic circulation [28]. 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). ; WritingOriginal Draft Preparation, S.G.-Z., M.G.-A., A.F.-Q., I.E. Consequently, isoflavones can have estrogenic or anti-estrogenic effects [3]. Dietary intake of flavonoid subclasses and risk of colorectal cancer: Evidence from population studies. In the same line, in European men, isoflavone concentrations did not affect the risk of developing prostate cancer. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. (2016), nine studies addressed to menopausal women and focused on bone health were analyzed [52]. 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. (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]. In addition, Qiu et al. In fact, all the body fluids, as the tides, were controlled by the lunar phases. Acid rain leaches aluminum from the soil. The authors found a significant inverse association between isoflavone intake and both overall mortality and breast cancer recurrence. It has been described that after the oral intake of isoflavones, their peak plasma concentration in humans occurs at around seven hours [33]. Xu B., Chibber R., Ruggiero D., Kohner E., Ritter J., Ferro A., Ruggerio D. Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products. The .gov means its official. Isoflavone excretion occurs mainly through urine and feces, primarily in the conjugate forms, and up to 95% takes place in 24 h [43]. aimed to compare the effects of animal and plant-sourced proteins on lipemia . In contrast, the effects on bone resorption biomarkers were more favorable in overweight or obese women than in women with a healthy weight. 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 dose of isoflavones ranged from 30 to 200 mg/day. Ko K.P., Kim C.S., Ahn Y., Park S.J., Kim Y.J., Park J.K., Lim Y.K., Yoo K.Y., Kim S.S. van der Schouw Y.T., Kreijkamp-Kaspers S., Peeters P.H., Keinan-Boker L., Rimm E.B., Grobbee D.E. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. As with other phenolic compounds, isoflavones can be presented as free forms (aglycones) or conjugated with carbohydrates (glycosides). Potential mechanism of action of isoflavones on bone metabolism. (2015), the authors examined the efficacy of phytoestrogens in reducing hot flushes [86]. For their meta-analysis, Jiang et al. The authors found, in a small number of studies (17 studies including 337 healthy, diabetic or hypercholesterolemic individuals), that a soy protein-based diet (rich in isoflavones) as compared to animal protein-based diets (meat, milk, casein, whey) resulted in reduced total cholesterol or LDL-cholesterol concentrations, increased HDL cholesterol concentrations, improved LDL:HDL cholesterol ratio, and decreased triglycerides. However, a limitation in this field is that there is still a great heterogeneity among studies. However, the magnitude of risk reduction in Asian women was slightly larger than in non-Asian women (22% vs. 18%). This fact was not taken into account in previous meta-analyses, and thus it may justify the discrepancies amongst them. 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]. Comparative efficacy of nonhormonal drugs on menopausal hot flashes. This meta-analysis included 266,699 participants (21,612 patients with prostate cancer among them). (2016) conducted a meta-analysis aimed at ovarian cancer, which affects women exclusively [74]. In miso and tempeh, the aglycone form is the most abundant one [9]. 1Nutrition and Obesity Group, Department of Pharmacy and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, 01006 Vitoria, Spain; sue.uhe@zemog.aoias (S.G.-Z. The conclusion was that isoflavones exerted little influence over bone mineral density and thus over bone health during menopause, although not all the studies observed the same effect. Similarly, Li 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. In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. 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. The authors suggested that further studies grouping subjects by isoflavone intake or by the circulating isoflavone levels might enhance this association. However, the results do not seem entirely conclusive, for there are discrepancies among the studies, probably related to their experimental designs. The main forms of conjugates in soybeans are the malonyl derivatives [14]. 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]. 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. As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. For the development of this section, the meta-analyses and systematic reviews published between 2015 and 2020 were taken into account. 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]. Urinary isoflavonoid excretion in humans is dose dependent at low to moderate levels of soy-protein consumption. However, the authors suggested that more prospective cohort studies are needed to further investigate this association and that the quantity of isoflavone intake should be accurately measured because flavonoid contents in food can vary significantly. In addition, genistein and glycitein are transformed into dihydrogenistein and dihydroglycitein, respectively, before being further converted into other metabolites. Hua X., Yu L., You R., Yang Y., Liao J., Chen D. Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis. Plants grow best when the moon is in the waxing phase, when its gravitational pull is strongest. With regard to prostate cancer, it has been proposed that it might be affected by isoflavone consumption due to its effect on hormone metabolism. Isoflavones are found in several vegetables, mainly in legumes (Fabaceae family) such as soy, white and red clover, alfalfa and beans [9,10]. 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. 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. Jun S., Shin S., Joung H. Estimation of dietary flavonoid intake and major food sources of Korean adults. [12,42]. Furthermore, isoflavones are associated with proteins; thus, alcohol extraction and processing diminish isoflavone content in foodstuffs such as fermented soybean, tofu or soy beverages. Barnes S. The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. Isoflavone Supplements for Menopausal Women: A Systematic Review. He X., Sun L.M. Chang H.H., Robinson A.R., Common R.H. Excretion of radioactive diadzein and equol as monosulfates and disulfates in the urine of the laying hen. Despite the positive effect of isoflavones, the authors emphasized that the effects took a long time to appear. 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. Association between Dietary Isoflavones in Soy and Legumes and Endometrial Cancer: A Systematic Review and Meta-Analysis. 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. Sex and long-term soy diets affect the metabolism and excretion of soy isoflavones in humans. 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]. (2016) included 17 studies (nine case-control studies and eight cohort studies) [80]. The work reported by Lambert et al. 8600 Rockville Pike (2019), included 16 prospective cohort studies involving 11,169 breast cancer cases and 648,913 participants [70]. (2016) published a meta-analysis of 13 case-control and four prospective cohort studies, where the results revealed that soy isoflavone consumption reduced the risk of developing colorectal cancer by 23% [79]. Karr S.C., Lampe J.W., Hutchins A.M., Slavin J.L. (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]. Lastly, Abshirini et al. They observed that it was dose-dependent at low to moderate soybean consumption. The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. The four chemical forms of the three most abundant isoflavones. After this, each metabolite undergoes its own metabolic pathway [40]. Federal government websites often end in .gov or .mil. 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. 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. Juglans regia L. is a traditional plant that has been integrated into traditional medicine since ancient times. In the same line, Yu et al. Ten studies reported a significant reduction in hot flush frequency in the phytoestrogen group when compared with the placebo group. The enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. Four meta-analyses have been reported to address this issue. 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]. In the end, isoflavones could be useful in reducing hot flushes associated with menopause. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. Isoflavones (high dose: 0.675.5 mg/day; and low dose: 0.0120.1 mg/day). 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. The results showed that a higher regular intake of foods rich in isoflavones might potentially decrease colorectal cancer incidence. ); sue.uhe@zednanref.oderfla (A.F.-Q. Wang X., Dykens J.A., Perez E., Liu R., Yang S., Covey D.F., Simpkins J.W. 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. 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. 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