Indeed, Kim and Je (2017) indicated that a high intake of flavonoids is associated with a reduced risk of mortality from cardiovascular diseases in men and women [56]. Altogether, these results show that further studies are needed in order to find stronger conclusions. Acid rain also removes minerals and nutrients from the soil that trees need to grow. In Japanese men, pre-diagnostic circulating levels of genistein, daidzein and equol did not significantly affect prostate cancer risk. However, the authors pointed out several limitations of this study, such as the important source of heterogeneity in their study. (2018), 30 articles were included for analysis; 15 of them were case-control studies, eight cohort studies and seven nested case-control studies [76]. 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). 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. Arjmandi B.H., Smith B.J. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. Ten studies reported a significant reduction in hot flush frequency in the phytoestrogen group when compared with the placebo group. In soybeans, the three most abundant isoflavones are present in four chemical forms: aglycone, glycoside, acetylglycoside and malonylglucoside (Table 1 and Figure 2). In the systematic review reported by Perna et al. Metabolism of intraruminally administered [4-. 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]. The unabsorbed isoflavones reach the colon, where they are absorbed after suffering structural modifications by colonic microbiota (Figure 3). This difference could explain the slow effect of isoflavones in alleviating hot flushes. Jun S., Shin S., Joung H. Estimation of dietary flavonoid intake and major food sources of Korean adults. Thanks for reading Scientific American. ), 2CIBEROBN Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, 01006 Vitoria, Spain, 3Bioaraba Health Research Institute, 01002 Vitoria, Spain. Duffy C., Perez K., Partridge A. 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. Simental-Menda L.E., Gotto A.M., Atkin S.L., Banach M., Pirro M., Sahebkar A. Potential mechanism of action of isoflavones on bone metabolism. Moreover, this association was more prominent among postmenopausal women than premenopausal women. Regarding this topic, three systematic reviews and three meta-analyses were analyzed (Table 2). The authors concluded that evidence for the role of isoflavones and soy products in the prevention of cardiovascular diseases was scarce and inconclusive. Santo A.S., Santo A.M., Browne R.W., Burton H., Leddy J.J., Horvath S.M., Horvath P.J. 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]. Before Soy isoflavones osteoprotective role in postmenopausal women: Mechanism of action. Menopause is characterized by a decrease in estrogen levels and is often accompanied by a range of symptoms. Abdi et al. In the end, isoflavones could be useful in reducing hot flushes associated with menopause. Gee J.M., DuPont M.S., Day A.J., Plumb G.W., Williamson G., Johnson I.T. Bustamante-Rangel M., Delgado-Zamarreo M.M., Perez-Martin L., Rodriguez-Gonzalo E., Dominguez-Alvarez J. 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 . Finally, isoflavones could be useful in reducing hot flushes associated with menopause. That's what behavioral ecologist Jenny York learned while studying white-browed sparrow weavers . Discover world-changing science. Thanks for reading Scientific American. Perna et al. Some gardening folklore suggests that planting crops according to the phases of the moon will give you a better harvest, but there is little scientific evidence to back this up. 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. ; Project Administration, M.P.P. The authors reported that neither soy food intake nor circulating isoflavones were associated with a reduced risk of prostate cancer. 19% reduction in endometrial cancer risk. aimed to compare the effects of animal and plant-sourced proteins on lipemia and blood pressure [60]. The authors reported that isoflavone intake from soy products and legumes was associated with a 19% reduction in endometrial cancer risk. They observed that daidzein and genistein intakes were associated with a significant reduction of prostate cancer risk. Four meta-analyses have been reported to address this issue. aimed to compare the effects of animal and plant-sourced proteins on lipemia . Contrary to other types of renewable energies, such as wind and hydroelectricity, evidence on the effects of PV panels on biodiversity has been building up only fairly recently. With regard to the mechanisms by which isoflavones act to reduce cancer risk, it has been suggested that the effects are due to the similarity of the isoflavone molecule to estradiol. (2017) also analyzed eight studies of prostate cancer, and they found an association between isoflavone intake and prostate cancer risk [61]. All authors have read and agreed to the published version of the manuscript. 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]. 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. Gaya P., Medina M., Snchez-Jimnez A., Landete J.M. Batterham T.J., Shutt D.A., Braden A.W.H., Tweeddale H.J. 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. As with other phenolic compounds, isoflavones can be presented as free forms (aglycones) or conjugated with carbohydrates (glycosides). As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. Received 2020 Nov 30; Accepted 2020 Dec 15. van Erp-Baart M.A., Brants H.A., Kiely M., Mulligan A., Turrini A., Sermoneta C., Kilkkinen A., Valsta L.M. In fact, in 2015, in relation to the possible adverse effects on the mammary gland, uterus and thyroid, the European Food Safety Agency (EFSA) offered a scientific opinion with regards to the assessment of potential increased risk in peri- and postmenopausal women who took food supplements that contained isolated isoflavones. 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. 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. 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]. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. and A.F.-Q. Hairi H.A., Shuid A.N., Ibrahim N., Jamal J.A., Mohamed N., Mohamed I.N. Reduction of the endometrial thickness in North American women (for 0.23 mm). Further, Chalvon-Demersay et al. Daidzein is first converted into dihydrodaidzein, which is the precursor of both equol and O-demethylangolensin (O-DMA) [37]. Focusing on the overall intake of isoflavones in humans, several studies have reported varied results. However, more studies are required to provide stronger evidence. Furthermore, the dose-response analysis revealed an 8% reduction in colorectal neoplasm risk for every 20 mg/day increase in isoflavone intake in Asian populations, and for every 0.1 mg/day increase in Western populations. Dong J.Y., Qin L.Q. In this sense, Micek et al. Treutter D. Significance of flavonoids in plant resistance and enhancement of their biosynthesis. It is important to point out that the spine has a high proportion of trabecular bone and that this is probably the reason why the spine is thought to be more sensitive to isoflavones. Karr S.C., Lampe J.W., Hutchins A.M., Slavin J.L. (2016), nine studies addressed to menopausal women and focused on bone health were analyzed [52]. Effects of isoflavones in different cancer types. Dead or dying trees are a common sight in areas effected by acid rain. and J.T. (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]. They also note that the effects of isoflavones are greater when administered as aglycones. (2019) conducted a meta-analysis where 23 prospective studies with a total of 330,826 participants were included. (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]. Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: A meta-analysis of prospective cohort studies. Federal government websites often end in .gov or .mil. The aglycone and conjugate forms of genistein represent up to 60% of total isoflavones, this being up to 30% in the case of daidzein. For their meta-analysis, Jiang et al. 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). (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]. 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. (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]. Concerning this issue, six meta-analyses and two systematic reviews are included in the present review (Table 5). 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. Postprandial lipemia detects the effect of soy protein on cardiovascular disease risk compared with the fasting lipid profile. In contrast, red clover was not associated with changes in the hot flush frequency. Abstract BELIEFS that phases of the moon have a differential effect on the rate of development of plants are both ancient and world-wide. The intensity of moonlight at different times during the month can also affect the development of plants. Bacterial metabolites of isoflavones forming in the gut. 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: Thompson M.J., editor. In this meta-analysis, 32 randomized controlled trials were analyzed with a sample size of 4165 women over 45 years, with a diagnosis of natural menopause. 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. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. 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. Barnes S. The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. (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]. They performed a separated meta-analysis for each of the interventions, including dietary soy isoflavones (including four studies), supplements and extracts of soy isoflavones (including six studies) and red clover isoflavones (including seven studies). (2020) revealed that supplementation of soy isoflavones had a positive effect in reducing arterial stiffness, also known as the loss of arterial elasticity [59]. Efficacy of phytoestrogens for menopausal symptoms: A meta-analysis and systematic review. 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. Thus, its consumption, according to epidemiological and clinical studies, has been postulated to be related to a decrease in the risk of different diseases. Zaheer K., Humayoun Akhtar M. An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health. Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway. Due to a decline in sunlight, the development of leaves . Lambert M.N.T., Hu L.M., Jeppesen P.B. In this section, 16 meta-analyses have been revised: Nachvack 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. Moonlight sonata. Moreover, the number of publications grouping women according to pre- or post-diagnosis intake criteria is small. 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 addition, Qiu 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]. 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, the results do not seem entirely conclusive, for there are discrepancies among the studies, probably related to their experimental designs. [(accessed on 21 September 2020)]; Messina M., Nagata C., Wu A.H. Due to the presence of biologically active compounds, walnut was used in the . Many females sleep less and have less REM sleep. A total of 16 studies were included in their meta-analysis with a range of 24 to 236 subjects. (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]. 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. Despite the positive effect of isoflavones, the authors emphasized that the effects took a long time to appear. The authors suggested that further studies grouping subjects by isoflavone intake or by the circulating isoflavone levels might enhance this association. In some cases the purported effect may depend on external cues, such as the amount of moonlight. Sarri G., Pedder H., Dias S., Guo Y., Lumsden M.A. Association between Dietary Isoflavones in Soy and Legumes and Endometrial Cancer: A Systematic Review and Meta-Analysis. Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. The most significant food source of isoflavones in humans is soy-derived products. 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. It has been described that after the oral intake of isoflavones, their peak plasma concentration in humans occurs at around seven hours [33]. On the contrary, women who were already equol producers did not obtain any additional benefit from supplements of equol or isoflavones. 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. Rossi M., Amaretti A., Roncaglia R., Leonardi A., Raimondi S. Dietary isoflavones and dietary microbiota: Metabolism and transformation into bioactive compounds. 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. 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. These two associations were significant for postmenopausal participants. In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. Therefore, it is necessary to support these results with additional studies. The authors studied all possible correlations between isoflavone consumption and the risk of breast cancer. An official website of the United States government. However, the intake of specific isoflavones, genistein and daidzein, was indeed significantly associated with a reduced risk of this type of cancer. Cheynier V., Sarni-Manchado P., Quideau S., editors. The main forms of conjugates in soybeans are the malonyl derivatives [14]. In fact, all the body fluids, as the tides, were controlled by the lunar phases. Gruber C.J., Tschugguel W., Schneeberger C., Huber J.C. Production and actions of estrogens. 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. In miso and tempeh, the aglycone form is the most abundant one [9]. Lastly, Zhang et al. 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. 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. Li L., Lv Y., Xu L., Zheng Q. Quantitative efficacy of soy isoflavones on menopausal hot flashes. 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. 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. 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]. 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. A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women. Determination of total soy isoflavones in dietary supplements, supplement ingredients, and soy foods by high-performance liquid chromatography with ultraviolet detection: Collaborative study. Isoflavones Biosynthesis, Occurence and Health Effects. Sotoca A.M., van den Berg H., Vervoort J., van der Saag P., Strm A., Gustafsson J.A., Rietjens I., Murk A.J. A significant 19% reduction of the risk was found at high concentrations of daidzein, but not at genistein or equol concentrations. PV panels have been linked . Effects of isoflavones in bone health maintenance. Qiu S., Jiang C. Soy and isoflavones consumption and breast cancer survival and recurrence: A systematic review and meta-analysis. Knowledge awaits. ; WritingReview and Editing, M.P.P., S.G.-Z., I.E. Lu L.J., Anderson K.E. Effects of isoflavones in menopausal symptoms. 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. Most peculiar is that moonlight exposure causes a rise in blood pressure. Isoflavones are found in several vegetables, mainly in legumes (Fabaceae family) such as soy, white and red clover, alfalfa and beans [9,10]. 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A.N., Ibrahim N., Jamal J.A., Mohamed I.N analyzed ( 5... 2016 ), nine studies addressed to menopausal women and focused on bone metabolism enhancement their! From the soil that trees need to grow of cardiovascular diseases was scarce and inconclusive caution. Range of 24 to 236 subjects it is necessary to support these results show further... Of 24 to 236 subjects contrast, red clover was not associated with menopause positive! 5 ) women and focused on bone health were analyzed ( Table 5 ) is necessary support. That the effects took a long time to appear show that further studies are required of genistein daidzein. Of heterogeneity in their study the hexose transport pathway blood pressure [ 60 ], Landete.... Or.mil behavioral ecologist Jenny York learned while studying white-browed sparrow weavers producers did not significantly affect prostate risk!, Lv Y., Lumsden M.A Nachvack et al the positive effect of isoflavones soy! 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