Zaheer K., Humayoun Akhtar M. An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health. ; WritingOriginal Draft Preparation, S.G.-Z., M.G.-A., A.F.-Q., I.E. 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. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. The work reported by Lambert et al. Hua et al. 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. In addition, it is important to highlight that interindividual differences in gut bacterial populations are responsible for the diverse effects of isoflavones in humans. 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. There are a total of 15 3 = 3375 possible outcomes. Moonlight sonata. 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. 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]. 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. 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. (2020) revealed that supplementation of soy isoflavones had a positive effect in reducing arterial stiffness, also known as the loss of arterial elasticity [59]. Moreover, Rienks et al. The enzyme lactase-phlorizin hydrolase (LPH) deglycosylases phenolic compounds in the intestinal lumen, and after that, the aglycone form enters the epithelial cells by passive diffusion. The meta-analysis included 15 studies in which the number of participants ranged from 30 to 252. 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. (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]. The four chemical forms of the three most abundant isoflavones. and J.T. 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. 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. 2023 Scientific American, a Division of Springer Nature America, Inc. While equol production seems to be similar in animals, it is very variable in humans [41], and therefore, beneficial effects referred to equol have been observed only in individuals with a specific microbiota composition [38]. Endometrial cancer (Table 4), as well as breast cancer, is an estrogen-dependent cancer type related to high circulating estradiol concentrations. By Marie If you're a gardener, you know that the moon cycles affect plant growth. Schmidt M., Arjomand-Wlkart K., Birkhuser M.H., Genazzani A.R., Gruber D.M., Huber J., Klbl H., Kreft S., Leodolter S., Linsberger D., et al. Although results vary greatly, most of these applications are supported by at least a few clinical studies. Global climate change is not a future problem. [(accessed on 21 September 2020)]; Messina M., Nagata C., Wu A.H. The effect of soy isoflavones on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials. Knowledge awaits. Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: A meta-analysis of prospective cohort studies. Day A.J., Caada F.J., Daz J.C., Kroon P.A., Mclauchlan R., Faulds C.B., Plumb G.W., Morgan M.R., Williamson G. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. Of those, 35 have 4 / 3, which can be demonstrated by having a computer generate the 3375 combinations and count those that satisfy the criterion.Therefore, by chance alone, one would expect 35/3375 or about 1/96 studies to exhibit as good a coincidence with the full moon as that observed by the authors. The six meta-analyses show a slight improvement in the frequency and intensity of hot flushes. Collison M.W. In this systematic review, 123 studies were included, with a total number of 516,330 participants. Moreover, this association was more prominent among postmenopausal women than premenopausal women. Another meta-analysis, conducted by Zhao et al. Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells. Li L., Lv Y., Xu L., Zheng Q. Quantitative efficacy of soy isoflavones on menopausal hot flashes. Zhong X.S., Ge J., Chen S.W., Xiong Y.Q., Ma S.J., Chen Q. In contrast, the effects on bone resorption biomarkers were more favorable in overweight or obese women than in women with a healthy weight. Future research in this field should quantify isoflavones as accurately as possible, analyzing larger cohorts and lengthening the follow-up stage. However, the authors pointed out several limitations of this study, such as the important source of heterogeneity in their study. Among the wide variety of flavonoids, isoflavones are one of the most renowned. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. These positive effects were associated with 54 mg/day of genistein and 600 mg/day of synthetic isoflavone ipriflavone. The difference for isoflavones required to find an effect can be due to variations in the amount of isoflavone intake between both populations. This fact suggests that other components, such as fiber in the soy foods, may account for these negative associations. On the contrary, women who were already equol producers did not obtain any additional benefit from supplements of equol or isoflavones. Ten studies reported a significant reduction in hot flush frequency in the phytoestrogen group when compared with the placebo group. Dietary polyphenol intake in Europe: The European Prospective Investigation into Cancer and Nutrition (EPIC) study. Proof by rational experiment seems to have been. 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. 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. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. 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. 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]. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. Isoflavones Biosynthesis, Occurence and Health Effects. Due to the presence of biologically active compounds, walnut was used in the . 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). 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. 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]. In the meta-analysis reported by Chen et al. In the meta-analysis reported by Applegate et al. . Bustamante-Rangel M., Delgado-Zamarreo M.M., Perez-Martin L., Rodriguez-Gonzalo E., Dominguez-Alvarez J. 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. Barnes S. The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. All authors have read and agreed to the published version of the manuscript. Chadha R., Bhalla Y., Jain A., Chadha K., Karan M. Dietary Soy Isoflavone: A Mechanistic Insight. Morning 3: Temp 98.6 BP 124/83 Pulse 62 bpm. (2018) revised 13 epidemiologic studies involving 178,947 participants: 7067 cases and 171,880 controls; among them, three were prospective cohort studies, and ten were population-based case-control studies [71]. The aglycone and conjugate forms of genistein represent up to 60% of total isoflavones, this being up to 30% in the case of daidzein. Vlachopoulos C., Aznaouridis K., Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: A systematic review and meta-analysis. Saloniemi H., Whl K., Nyknen-Kurki P., Kallela K., Saastamoinen I. Phytoestrogen content and estrogenic effect of legume fodder. This fact was not taken into account in previous meta-analyses, and thus it may justify the discrepancies amongst them. Create your free account or Sign in to continue. Two meta-analyses, which covered prospective cohort studies, showed that soy isoflavone consumption was not associated significantly with mortality linked to cardiovascular events [56,62]. (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]. 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. You J., Sun Y., Bo Y., Zhu Y., Duan D., Cui H., Lu Q. Even though red clover has a greater amount of isoflavones, it is not an edible plant, and it is consumed as a food complement. Kelly G.E., Nelson C., Waring M.A., Joannou G.E., Reeder A.Y. Dong J.Y., Qin L.Q. 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]. Thus, soybean can be considered as the best food source. The main forms of conjugates in soybeans are the malonyl derivatives [14]. Nevertheless, the results do not seem entirely conclusive, as there are discrepancies among the studies included in the systematic reviews and in the meta-analyses, probably related to their experimental designs. Moreover, sodium-dependent glucose transporter 1 (SGLT1) allows phenolic compound-glycosylates to directly enter into epithelial cells, where they are hydrolyzed by cytosolic glucosidases [30,31]. (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. Beneficial role of dietary phytoestrogens in obesity and diabetes. [12,42]. 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. and Rossi et al. 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. Isoflavone content in soy-derived products is usually lower than in soybeans [17]. (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]. Jun S., Shin S., Joung H. Estimation of dietary flavonoid intake and major food sources of Korean adults. In contrast, red clover was not associated with changes in the hot flush frequency. Franco et al. Potential mechanism of action of isoflavones on bone metabolism. 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. As in the case of other phenolic compounds, genistein and daidzein undergo phase II xenobiotic metabolism, mainly glucuronidation and sulfation reactions at 4and/or 7 positions of the isoflavone ring [34,35]. Acid rain also removes minerals and nutrients from the soil that trees need to grow. Liu J., Yuan F., Gao J., Shan B., Ren Y., Wang H., Gao Y. Further, Chalvon-Demersay et al. As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. and J.T. Vasomotor symptoms resulting from natural menopause: A systematic review and network meta-analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause. Potential health adverse effects in the intake of isoflavones have been postulated due to their estrogenic activity, especially in relation to breast cancer. 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. 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. 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]. So long ago as 1880 Siemens showed that continuous exposure to arc lamps promoted luxuriance of foliage . The authors found a significant inverse association between isoflavone intake and both overall mortality and breast cancer recurrence. (2016) conducted a meta-analysis of 18 studies involving 16,917 colorectal cancer cases in 559,486 participants [78]. Gee J.M., DuPont M.S., Day A.J., Plumb G.W., Williamson G., Johnson I.T. They also explained that the differences between isoflavones and the rest of the drugs might be because the latter act by modulating central neurotransmitters and, as a consequence, by regulating the central thermoregulatory centers in the hypothalamus. Acid rain leaches aluminum from the soil. He et al. 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. 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]. Consensus: Soy isoflavones as a first-line approach to the treatment of menopausal vasomotor complaints. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Abdi 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]. Prez-Cornago et al. Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. Abstract BELIEFS that phases of the moon have a differential effect on the rate of development of plants are both ancient and world-wide. 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