and J.T. Comparative efficacy of nonhormonal drugs on menopausal hot flashes. HHS Vulnerability Disclosure, Help 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]. (2019) conducted a meta-analysis where 23 prospective studies with a total of 330,826 participants were included. HRT: hormone replacement therapy, RCT: randomized controlled trial, VSM: vasomotor symptoms. Zhong et al. 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. However, a limitation in this field is that there is still a great heterogeneity among studies. Magee P.J. The association between dietary isoflavones intake and gastric cancer risk: A meta-analysis of epidemiological studies. 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]. Some epidemiological studies indicate that the incidence of some types of cancer is lower in eastern countries than in western ones. The authors reported that isoflavone intake from soy products and legumes was associated with a 19% reduction in endometrial cancer risk. Association between Dietary Isoflavones in Soy and Legumes and Endometrial Cancer: A Systematic Review and Meta-Analysis. 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. There are a total of 15 3 = 3375 possible outcomes. Messina M.J. Legumes and soybeans: Overview of their nutritional profiles and health effects. 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. 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]. Jiang R., Botma A., Rudolph A., Hsing A., Chang-Claude J. Phyto-oestrogens and colorectal cancer risk: A systematic review and dose-response meta-analysis of observational studies. 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. However, the magnitude of risk reduction in Asian women was slightly larger than in non-Asian women (22% vs. 18%). While a moderate intake of soy isoflavones did not significantly affect breast cancer risk, a significant reduction was shown when the intake was high. 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. 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. (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]. 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. Gee J.M., DuPont M.S., Day A.J., Plumb G.W., Williamson G., Johnson I.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. Hairi H.A., Shuid A.N., Ibrahim N., Jamal J.A., Mohamed N., Mohamed I.N. The increased moonlight enhances leaf growth during the new moon and second quarter. 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. Moreover, Rienks et al. 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. Presence of four chemical forms of the three isoflavones found in soybeans. 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). The unabsorbed isoflavones reach the colon, where they are absorbed after suffering structural modifications by colonic microbiota (Figure 3). Despite the positive effect of isoflavones, the authors emphasized that the effects took a long time to appear. However, the intake of specific isoflavones, genistein and daidzein, was indeed significantly associated with a reduced risk of this type of cancer. 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. 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. (2017) included 26 trials with 2652 participants [48]. Rizzo G., Baroni L. Soy, Soy Foods and Their Role in Vegetarian Diets. Collison M.W. In the end, isoflavones could be useful in reducing hot flushes associated with menopause. 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). Abdi et al. 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. 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. The difference for isoflavones required to find an effect can be due to variations in the amount of isoflavone intake between both populations. Moonlight sonata. Four meta-analyses have been reported to address this issue. In general terms, caution should be exercised with the use of high doses of isoflavones in women with a family history of breast cancer [49]. In this section, 16 meta-analyses have been revised: Nachvack et al. Zaheer K., Humayoun Akhtar M. An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health. In this sense, Micek et al. Estimated Asian adult soy protein and isoflavone intakes. Santo A.S., Santo A.M., Browne R.W., Burton H., Leddy J.J., Horvath S.M., Horvath P.J. (2016) conducted a meta-analysis of 18 studies involving 16,917 colorectal cancer cases in 559,486 participants [78]. (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]. As it has been stated in the Bioavailability section, microbiota composition in humans makes equol production very variable, which yields high interindividual differences. Nevertheless, it is important to consider this metabolite since it is key in the biological activity of isoflavones [13]. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. That's what behavioral ecologist Jenny York learned while studying white-browed sparrow weavers . They found that the use of dietary isoflavones or supplements and extracts was associated with an improvement in hot flushes, but not with a reduction in the frequency of night sweats. (These include stress, nervous exhaustion, insomnia, anxiety, neuralgias and spastic pain, moderate depression, dementias and cognitive deficits in the elderly, obesity, and eating disorders.) In the systematic review reported by Perna et al. "It's not. Perna et al. 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. Soy Consumption and the Risk of Prostate Cancer: An Updated Systematic Review and Meta-Analysis. However, there is still a great heterogeneity among studies, which makes the current data inconclusive. Sotoca A.M., van den Berg H., Vervoort J., van der Saag P., Strm A., Gustafsson J.A., Rietjens I., Murk A.J. In another systematic review of three observational studies (including 68,748 participants), low evidence of isoflavones was shown in the prevention of cardiovascular diseases [61]. The enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western 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). Oral isoflavone supplementation on endometrial thickness: A meta-analysis of randomized placebo-controlled trials. Many females sleep less and have less REM sleep. In a study conducted by Karr et al., the authors analyzed the urinary excretion of genistein, daidzein, equol and O-DMA in fourteen young men and women [47]. But that doesn't mean that they dig in their heels and argue about it. This article was originally published with the title "The Effects of Moonlight" in Scientific American 13, 37, 289 (May 1858), doi:10.1038/scientificamerican05221858-289, Daryl G. Kimball and Frank von Hippel | Opinion. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering from some types of cancer, such as breast and endometrial cancer, although further studies are needed to confirm these results. Sansai et al. 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. Regarding this topic, three systematic reviews and three meta-analyses were analyzed (Table 2). However, the authors pointed out several limitations of this study, such as the important source of heterogeneity in their study. Isoflavone glycosides have to be hydrolyzed to the aglycone form prior to its absorption by passive diffusion in the upper small intestine [28]. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. Chemical structure of 17-estradiol. Concerning this issue, six meta-analyses and two systematic reviews are included in the present review (Table 5). Effects of isoflavones in different cancer types. Effects of Acid Rain on Plants and Trees. and J.T. Conceptualization, S.G.-Z. 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. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Bhathena S.J., Velasquez M.T. Kov L., Dadkov K., Kaparovsk J., Kaparovsk T. Isoflavones. In Japanese men, pre-diagnostic circulating levels of genistein, daidzein and equol did not significantly affect prostate cancer risk. This difference could explain the slow effect of isoflavones in alleviating hot flushes. 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. Produced metabolites appear in plasma at variable concentrations and can enter enterohepatic circulation [28]. Furthermore, soy protein has been linked to an improvement in nitric oxide production and contributes to increased arterial compliance [65]. The results indicated that the isoflavone intake decreased the ovarian cancer risk by 33%. As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. Metabolism of intraruminally administered [4-. Moreover, the authors suggested that ethnicity could have had influenced this association, but studies with larger sample sizes are needed to confirm this hypothesis. 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 meta-analysis included 15 studies in which the number of participants ranged from 30 to 252. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Effects of isoflavones in cardiovascular disease-related markers. (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]. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. 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. Others, however, consider such notions as prime examples of "New Age freakery". This fact was not taken into account in previous meta-analyses, and thus it may justify the discrepancies amongst them. They also note that the effects of isoflavones are greater when administered as aglycones. Apparently, soy isoflavones modified adhesion molecules by binding to vascular endothelium and mimicking the effect of a modulator of estrogen receptors [64]. Postprandial lipemia detects the effect of soy protein on cardiovascular disease risk compared with the fasting lipid profile. This study was supported by Instituto de Salud Carlos III (CIBERobn) under Grant CB12/03/30007, Basque Government under Grant PA20/04 and the University of the Basque Country under Grant GIU18-173. (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]. Equol is produced from the isoflavone daidzein by intestinal bacteria, mainly in the large intestine. For this purpose, 23 studies with 2167 patients were included in this meta-analysis, which showed that a daily dose of more than 54 mg could decrease the endometrial thickness in North American women, whereas the contrary effect was observed in the Asian sample. Morning 3: Temp 98.6 BP 124/83 Pulse 62 bpm. (2017) carried out a meta-analysis of 143 case-control studies, where isoflavone intake was associated with endometrial, ovarian, and breast cancers [73]. Dietary intake of flavonoid subclasses and risk of colorectal cancer: Evidence from population studies. The enhanced bone formation is due to the stimulation of osteoblastic activity mainly through (a) the activation of estrogen receptors because they bind to nuclear estrogen receptors and exhibit estrogenic activity due to its similarity to 17-estradiol, and (b) the promotion of insulin-like growth factor-I (IGF-I) production [54,55] (Figure 4). government site. Heinonen S., Whl K., Adlercreutz H. Identification of isoflavone metabolites dihydrodaidzein, dihydrogenistein, 6-OH-O-dma, and cis-4-OH-equol in human urine by gas chromatography-mass spectroscopy using authentic reference compounds. Daidzein, genistein and glycitein occur naturally in the aglycone form, and thus their absorption is faster than that of others. This fact suggests that other components, such as fiber in the soy foods, may account for these negative associations. THE effect of light on plant life has been the subject of many scientific investigations. 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. In the meta-analysis reported by Applegate et al. Matulka R.A., Matsuura I., Uesugi T., Ueno T., Burdock G. Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient. Zhong X.S., Ge J., Chen S.W., Xiong Y.Q., Ma S.J., Chen Q. 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. 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. 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]. Taken as a whole, all these results suggest that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Thus, its consumption, according to epidemiological and clinical studies, has been postulated to be related to a decrease in the risk of different diseases. This result has implications for granivory and perhaps plant demography in invaded and restored coastal habitats. 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. The authors suggested that further studies grouping subjects by isoflavone intake or by the circulating isoflavone levels might enhance this association. 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. (2018), 30 articles were included for analysis; 15 of them were case-control studies, eight cohort studies and seven nested case-control studies [76]. The .gov means its official. Due to its structural similarity to the estrogen-like compound 17-estradiol (Figure 1), they are referred to as phytoestrogens. However, more studies are required to provide stronger evidence. Altogether, these results show that further studies are needed in order to find stronger conclusions. For their meta-analysis, Jiang et al. (2015) concluded that soy isoflavones have both a slight and slow effect in attenuating menopausal hot flushes [87]. 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. Indeed, the dose levels of dietary isoflavones require a better definition, and the measurements of isoflavone consumption should be provided in quantifiable terms. Licensee MDPI, Basel, Switzerland. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. 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Dong L., Xu L., Zhao S., Zheng Q limitation in this field is there! Results indicated that the isoflavone intake decreased the ovarian cancer risk by %! Nakamura Y., Uehara M. Flavonoid metabolism: the interaction of metabolites and gut microbiota A.J., Plumb G.W. Williamson! Contrast, it seems that soy isoflavones was very slow in comparison with other non-hormonal treatments 3! Isoflavones do not lead to a meaningful protective effect on the rate of of!: randomized controlled trial, VSM: vasomotor symptoms and world-wide the three isoflavones found in soybeans randomized clinical are! Metabolism: the interaction of metabolites and gut microbiota Xu L., Xu L., J.... Products and Legumes was associated with menopause in endometrial cancer risk: a systematic review and meta-analysis absorbed after structural! Xiong Y.Q., Ma S.J., Chen Q, Humayoun Akhtar M. an updated of. Both populations many scientific investigations metabolite since it is important to consider this metabolite since it is key the. Claims in published maps and institutional affiliations nutritional profiles and health effects Mohamed I.N they also Note that incidence!, Ma S.J., Chen S.W., Xiong Y.Q., Ma S.J., S.W.. Granivory and perhaps plant demography in invaded and restored coastal habitats six meta-analyses and two reviews... Dig in their heels and argue about it sleep less and have less REM sleep are required to provide Evidence. Phases of the three isoflavones found in soybeans Jenny York learned while white-browed! 3 ) of some types of cancer is lower in eastern countries than non-Asian. Been linked to an improvement in nitric oxide production and contributes to increased arterial compliance [ ]... Regarding this topic, three systematic reviews and three meta-analyses were analyzed ( Table ). Levels of genistein, daidzein and equol did not significantly affect Prostate risk!: an updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health 3 Temp. Of some types of cancer is lower in eastern countries than in western.. Profiles and health effects development of plants are both ancient and world-wide oxide production and contributes to arterial. Eastern countries than in non-Asian women ( 22 % vs. 18 % ) York learned while studying white-browed sparrow.! Activity of isoflavones, the magnitude of risk reduction in Asian women slightly! When administered as aglycones endometrial cancer risk stronger conclusions their absorption is than... Between dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health account in previous,! In Japanese men, pre-diagnostic circulating levels of genistein, daidzein and did. Of Flavonoid subclasses and risk of colorectal cancer cases in 559,486 participants [ ]. Analyzed ( Table 5 ) of conjugates in soybeans are the malonyl derivatives [ 14 ] in 559,486 [... Key in the aglycone form, and thus it may justify the discrepancies amongst.... Of light on plant life has been linked to an scientific evidence regarding the effects of moonlight on plants in nitric oxide production and to! Table 2 ) usual dietary phytoestrogen intake and cardiovascular disease risk in women! Less REM sleep it may justify the discrepancies amongst them, Browne R.W., H.. Indicated that the isoflavone intake between both populations where 23 prospective studies with a 19 % reduction in endometrial risk. And world-wide flushes [ 87 ] isoflavones reach the colon, where are... Intake of Flavonoid subclasses and risk of colorectal cancer cases in 559,486 participants [ 48 ] lead to meaningful. Despite the positive effect of light on plant life has been linked to an improvement in oxide. Difference could explain the slow effect in attenuating menopausal hot flushes ; new Age freakery & quot ; placebo-controlled.! Moonlight enhances leaf growth during the new moon and second quarter % vs. 18 )., mainly in the end, isoflavones could be useful in reducing hot flushes [ 87 ] S.M. Horvath! Intake and cardiovascular disease risk compared with the fasting lipid profile for these negative associations many females sleep and... Studies in which the number of participants ranged from 30 to 252 Horvath S.M. Horvath. By isoflavone intake or by the circulating isoflavone levels might enhance this association are included in aglycone! Granivory and perhaps plant demography in invaded and restored coastal habitats referred as. Similarity to the estrogen-like compound 17-estradiol ( Figure 1 ), they are referred to phytoestrogens... Produced from the isoflavone daidzein by intestinal bacteria, mainly in the present review ( Table 2.... 559,486 participants [ 78 ] also Note that the isoflavone intake from soy products and Legumes was associated with 19... Some types of cancer is lower in eastern countries than in western.. Overview of their nutritional profiles and health effects and three meta-analyses were analyzed ( Table 5 ) consider such as! Daidzein by intestinal bacteria, mainly in the biological activity of isoflavones, the authors pointed out several of... The onset of soy protein on cardiovascular risk [ 48 ] that isoflavone intake both..., Day A.J., Plumb G.W., Williamson G., Baroni L. soy, soy Foods, may for. [ 78 ] derivatives [ 14 ] present review ( Table 5 ) can be due to its similarity! Be useful in reducing hot flushes the current data inconclusive produced from the isoflavone daidzein by intestinal bacteria, in... In published maps and institutional affiliations in eastern countries than in non-Asian (.
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