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]. Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway. Although the mechanisms of action of isoflavones are not completely understood, it seems that isoflavones not only reduce the rate of bone resorption but also increase the rate of bone formation. The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. 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. 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 most significant food source of isoflavones in humans is soy-derived products. In this sense, the authors suggested that the composition of the gut microflora may influence isoflavone absorption and metabolism and could affect the production of isoflavone metabolites, which, in turn, could mediate their biological activity. 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). They also note that the effects of isoflavones are greater when administered as aglycones. (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]. For the development of this section, the meta-analyses and systematic reviews published between 2015 and 2020 were taken into account. The association between dietary isoflavones intake and gastric cancer risk: A meta-analysis of epidemiological studies. In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. Gut bacterial metabolism of the soy isoflavone daidzein: Exploring the relevance to human health. 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. 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. van Erp-Baart M.A., Brants H.A., Kiely M., Mulligan A., Turrini A., Sermoneta C., Kilkkinen A., Valsta L.M. Many females sleep less and have less REM sleep. Since hepatic lipase and lipoprotein lipase hydrolyze triglycerides into their constituents glycerol and fatty acids, their activation results in the delivery of the fatty acids to tissues such as muscle and adipose tissue. The authors suggested that further studies grouping subjects by isoflavone intake or by the circulating isoflavone levels might enhance this association. 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. (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]. Isoflavones are found in several vegetables, mainly in legumes (Fabaceae family) such as soy, white and red clover, alfalfa and beans [9,10]. 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. 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. Isoflavones have received attention due to their putative healthy properties. Regarding this topic, three systematic reviews and three meta-analyses were analyzed (Table 2). A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women. Morning 3: Temp 98.6 BP 124/83 Pulse 62 bpm. Zhong X.S., Ge J., Chen S.W., Xiong Y.Q., Ma S.J., Chen Q. . The authors suggested that this difference could be due to different genetic backgrounds and dietary patterns among Asian and Western populations. (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]. Bethesda, MD 20894, Web Policies The results showed that a higher regular intake of foods rich in isoflavones might potentially decrease colorectal cancer incidence. Lund S., Holman G.D., Schmitz O., Pedersen O. 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. Zaheer K., Humayoun Akhtar M. An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health. Adlercreutz H., Markkanen H., Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism. Acid rain leaches aluminum from the soil. Comparative efficacy of nonhormonal drugs on menopausal hot flashes. Modified from Wang et al., 2006 [4]. In fact, all the body fluids, as the tides, were controlled by the lunar phases. Possible mechanism of action of isoflavones for menopausal symptoms. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. sharing sensitive information, make sure youre on a federal Scientists often disagree about certain things. 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]. 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]. 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. It has been described that after the oral intake of isoflavones, their peak plasma concentration in humans occurs at around seven hours [33]. Mace T.A., Ware M.B., King S.A., Loftus S., Farren M.R., McMichael E., Scoville S., Geraghty C., Young G., Carson W.E., et al. Although results vary greatly, most of these applications are supported by at least a few clinical studies. 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]. The dose of isoflavones ranged from 30 to 200 mg/day. (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]. 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. 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]. (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]. Dietary polyphenol intake in Europe: The European Prospective Investigation into Cancer and Nutrition (EPIC) study. official website and that any information you provide is encrypted The effect of the moon on planting times is stated as a matter of fact in such popular publications as The Old Farmer's Almanac and books such as Gardening and Planting by the Moon 2018, and, of course, calendars such as The Biodynamic Sowing and Planting Calendar 2018. In the end, isoflavones could be useful in reducing hot flushes associated with menopause. 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]. The aglycone and conjugate forms of genistein represent up to 60% of total isoflavones, this being up to 30% in the case of daidzein. 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. The site is secure. Daily et al. However, the moonlight decreases after the full moon. 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. In tropical climates meat which is exposed to the moonlight rapidly becomes putrid ; and in the Indies, the negroes who will lie sweltering and unoovered beneath the full glare of a tropical sun, carefully muffle their heads and faces when exposed to the moonbeams, which they believe will cause swelling and distortion of the features, and sometimes even blindness. Isoflavone glycosides have to be hydrolyzed to the aglycone form prior to its absorption by passive diffusion in the upper small intestine [28]. Furthermore, isoflavones are able to inhibit aromatase activity, the enzyme that converts androgen to estrogen. 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]. (At least not real scientists.) 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. In the systematic review reported by Perna et al. 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. 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. ; Project Administration, M.P.P. This meta-analysis included 266,699 participants (21,612 patients with prostate cancer among them). 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. (2015), the authors examined the efficacy of phytoestrogens in reducing hot flushes [86]. Reduction of the endometrial thickness in North American women (for 0.23 mm). Implications of phytoestrogen intake for breast cancer. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. It follows that additional high-quality, large-scale randomized controlled trials are needed. Sfakianos J., Coward L., Kirk M., Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. Circulating isoflavone and lignan concentrations and prostate cancer risk: A meta-analysis of individual participant data from seven prospective studies including 2,828 cases and 5,593 controls. Global climate change is not a future problem. He X., Sun L.M. Kurzer M.S., Xu X. Dietary phytoestrogens. Anywise, it has been observed that both isoflavones are demethylated by microbiota, formononetin to daidzein and biochanin A to genistein. Among these, vasomotor symptoms comprising hot flushes and night sweats are the most common and bothersome, which, in turn, have a negative impact on womens quality of life. They observed that it was dose-dependent at low to moderate soybean consumption. Santo A.S., Santo A.M., Browne R.W., Burton H., Leddy J.J., Horvath S.M., Horvath P.J. Kim Y., Je Y. Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. Careers, Unable to load your collection due to an error. Another meta-analysis, conducted by Zhao et al. FOIA In this systematic review, 123 studies were included, with a total number of 516,330 participants. 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]. However, the magnitude of risk reduction in Asian women was slightly larger than in non-Asian women (22% vs. 18%). 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]. For this reason, the results should be interpreted with caution, and more randomized clinical trials are imperative. 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. Ronis M.J., Little J.M., Barone G.W., Chen G., Radominska-Pandya A., Badger T.M. The authors concluded that evidence for the role of isoflavones and soy products in the prevention of cardiovascular diseases was scarce and inconclusive. . For this reason, the bioavailability of isoflavones has been extensively characterized in animal models and humans [25,26,27]. 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. (2016) included 17 studies (nine case-control studies and eight cohort studies) [80]. ; WritingOriginal Draft Preparation, S.G.-Z., M.G.-A., A.F.-Q., I.E. With regard to prostate cancer, it has been proposed that it might be affected by isoflavone consumption due to its effect on hormone metabolism. After an extensive bibliographical review, the expert panel concluded that the results of observational studies do not support the hypothesis of an increased risk of breast cancer after isoflavone-rich food supplement intake [93]. Altogether, these results show that further studies are needed in order to find stronger conclusions. Postprandial lipemia detects the effect of soy protein on cardiovascular disease risk compared with the fasting lipid profile. THE effect of light on plant life has been the subject of many scientific investigations. Determination of total soy isoflavones in dietary supplements, supplement ingredients, and soy foods by high-performance liquid chromatography with ultraviolet detection: Collaborative study. (2018) performed a meta-analysis of 12 studies, where six were cohort studies, and six case-control studies, with a total of 596,553 participants [81]. 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. 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 six meta-analyses show a slight improvement in the frequency and intensity of hot flushes. Rienks et al. Before The enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. ); sue.uhe@zednanref.oderfla (A.F.-Q. However, there is still a great heterogeneity among studies, which makes the current data inconclusive. Isoflavones (high dose: 0.675.5 mg/day; and low dose: 0.0120.1 mg/day). 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. He et al. (2018), 30 articles were included for analysis; 15 of them were case-control studies, eight cohort studies and seven nested case-control studies [76]. By Marie If you're a gardener, you know that the moon cycles affect plant growth. In this study, five prospective cohort studies and seven case-control studies, with 6275 cases and 393,776 controls, were included. Lastly, Abshirini et al. Some epidemiological studies indicate that the incidence of some types of cancer is lower in eastern countries than in western ones. (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]. 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. After this, each metabolite undergoes its own metabolic pathway [40]. As with other phenolic compounds, isoflavones can be presented as free forms (aglycones) or conjugated with carbohydrates (glycosides). aimed to compare the effects of animal and plant-sourced proteins on lipemia . The lunar effect is a purported unproven correlation between specific stages of the roughly 29.5-day lunar cycle and behavior and physiological changes in living beings on Earth, including humans. aimed to compare the effects of animal and plant-sourced proteins on lipemia . An official website of the United States government. Oral isoflavone supplementation on endometrial thickness: A meta-analysis of randomized placebo-controlled trials. 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]. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. As it has been stated in the Bioavailability section, microbiota composition in humans makes equol production very variable, which yields high interindividual differences. 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. 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. Discover world-changing science. The .gov means its official. The difference for isoflavones required to find an effect can be due to variations in the amount of isoflavone intake between both populations. 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. In contrast, it seems that isoflavones do not act on central neurotransmitters directly. Modified from Mace et al. In addition, genistein and glycitein are transformed into dihydrogenistein and dihydroglycitein, respectively, before being further converted into other metabolites. Metabolites of dietary (soya) isoflavones in human urine. The main isoflavones found in foodstuffs are daidzein, genistein and glycitein, as well as biochanin A and formononetin [9,12]. 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. However, the authors pointed out several limitations of this study, such as the important source of heterogeneity in their study. Franco et al. They discuss their differences and resolve the discrepancies, if possible. In the meta-analysis reported by Applegate et al. That aluminum may be harmful to plants as well as animals. [12,42]. A significant 19% reduction of the risk was found at high concentrations of daidzein, but not at genistein or equol concentrations. Dong J.Y., Qin L.Q. Accessibility Presence of four chemical forms of the three isoflavones found in soybeans. Atkinson C., Frankenfeld C.L., Lampe J.W. 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. 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. Endometrial cancer (Table 4), as well as breast cancer, is an estrogen-dependent cancer type related to high circulating estradiol concentrations. 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]. 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. 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. Furthermore, among the four studies of breast cancer recurrence, three studies found that isoflavone intake decreased the risk of breast cancer recurrence, although further studies are required to confirm this finding [82]. Similarly, Li et al. Batterham T.J., Shutt D.A., Braden A.W.H., Tweeddale H.J. 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. Moreover, the number of publications grouping women according to pre- or post-diagnosis intake criteria is small. Juglans regia L. is a traditional plant that has been integrated into traditional medicine since ancient times. Chemical structure of 17-estradiol. (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]. 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]. 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. Moreover, the authors suggested that ethnicity could have had influenced this association, but studies with larger sample sizes are needed to confirm this hypothesis. Analysis of isoflavones in Foods. Liu J., Yuan F., Gao J., Shan B., Ren Y., Wang H., Gao Y. 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. The https:// ensures that you are connecting to the 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. Nachvak S.M., Moradi S., Anjom-Shoae J., Rahmani J., Nasiri M., Maleki V., Sadeghi O. Soy, Soy Isoflavones, and Protein Intake in Relation to Mortality from All Causes, Cancers, and Cardiovascular Diseases: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies. Beneficial role of dietary phytoestrogens in obesity and diabetes. National Library of Medicine Daidzein, genistein and glycitein occur naturally in the aglycone form, and thus their absorption is faster than that of others. Explore our digital archive back to 1845, including articles by more than 150 Nobel Prize winners. Bhathena S.J., Velasquez M.T. At high elevations, acidic fog and clouds might . we announced our decision to consider the exercise of our enforcement discretion relative to the declaration of eight more isolated or synthetic non-digestible carbohydrates as dietary fibers when . Background Climate change and the current phase-out of fossil fuel-fired power generation are currently expanding the market of renewable energy and more especially photovoltaic (PV) panels. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. In conclusion, this study reported some evidence that suggests the beneficial role that daidzein and genistein play in preventing breast cancer risk. Diversely, Liu et al. Moreover, Rienks et al. HHS Vulnerability Disclosure, Help 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. In fact, the number of isoflavones present was very variable among the different soy food types. In this sense, Micek et al. 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. Man B., Cui C., Zhang X., Sugiyama D., Barinas-Mitchell E., Sekikawa A. 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 latter is the most common form in foodstuffs, with the exception of fermented soy products, such as miso and tempeh. Treutter D. Significance of flavonoids in plant resistance and enhancement of their biosynthesis. 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]. In soybeans, the three most abundant isoflavones are present in four chemical forms: aglycone, glycoside, acetylglycoside and malonylglucoside (Table 1 and Figure 2). F., Gao Y the beneficial role that daidzein and genistein play in preventing breast cancer, is estrogen-dependent... Interaction of metabolites and gut microbiota meta-analyses were analyzed ( Table 4 ), the! Although not in cohort studies kim Y., Je Y. Flavonoid intake gastric! 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