In fact, all the body fluids, as the tides, were controlled by the lunar phases. Hosoda K., Furuta T., Yokokawa A., Ishii K. Identification and quantification of daidzein-7-glucuronide-4-sulfate, genistein-7-glucuronide-4-sulfate and genistein-4,7-diglucuronide as major metabolites in human plasma after administration of kinako. Regarding the mechanisms by which isoflavones act to alleviate vasomotor symptoms, is has been proposed that they bind to estrogen receptors and activate endothelial nitric oxide synthase (eNOS) transcription, leading to eNOS synthesis and nitric oxide production, the main mediator of vasodilatation, which allows cutaneous heat dissipation [91] (Figure 6). Bacterial metabolites of isoflavones forming in the gut. The https:// ensures that you are connecting to the The six meta-analyses show a slight improvement in the frequency and intensity of hot flushes. Sotoca A.M., van den Berg H., Vervoort J., van der Saag P., Strm A., Gustafsson J.A., Rietjens I., Murk A.J. Soy products (0.05130 g/day) and total isoflavones (0.28 to 63 mg/day). Moreover, the authors suggested that ethnicity could have had influenced this association, but studies with larger sample sizes are needed to confirm this hypothesis. 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]. Isoflavones Biosynthesis, Occurence and Health Effects. and J.T. 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. Global climate change is not a future problem. 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. 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. 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. 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]. 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]. Kurzer M.S., Xu X. Dietary phytoestrogens. Daily et al. Careers, Unable to load your collection due to an error. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. Gut bacterial metabolism of the soy isoflavone daidzein: Exploring the relevance to human health. On the contrary, women who were already equol producers did not obtain any additional benefit from supplements of equol or isoflavones. (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 enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. Gee J.M., DuPont M.S., Day A.J., Plumb G.W., Williamson G., Johnson I.T. Four meta-analyses have been reported to address this issue. In this sense, soy isoflavones have been proposed as beneficial because, in theory, they may contribute to the maintenance of good bone health (mass, mineral density and bone structure) in women who are at this stage in their life. In like manner, a meta-analysis by Simental-Menda et al. Proof by rational experiment seems to have been. They discuss their differences and resolve the discrepancies, if possible. The authors found a significant inverse association between isoflavone intake and both overall mortality and breast cancer recurrence. 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. Bustamante-Rangel M., Delgado-Zamarreo M.M., Perez-Martin L., Rodriguez-Gonzalo E., Dominguez-Alvarez J. 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 aglycone and conjugate forms of genistein represent up to 60% of total isoflavones, this being up to 30% in the case of daidzein. 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]. It has been described that after the oral intake of isoflavones, their peak plasma concentration in humans occurs at around seven hours [33]. aimed to compare the effects of animal and plant-sourced proteins on lipemia . Effects of isoflavones in different cancer types. Morning 3: Temp 98.6 BP 124/83 Pulse 62 bpm. (2016) conducted a meta-analysis aimed at ovarian cancer, which affects women exclusively [74]. Isoflavone intake in four different European countries: The VENUS approach. In miso and tempeh, the aglycone form is the most abundant one [9]. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. In addition, it is important to highlight that interindividual differences in gut bacterial populations are responsible for the diverse effects of isoflavones in humans. 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. 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. 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. He X., Sun L.M. However, the magnitude of risk reduction in Asian women was slightly larger than in non-Asian women (22% vs. 18%). official website and that any information you provide is encrypted 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. The authors indicated that no consensus was found regarding the protective effects of soy isoflavones (2080 mg) and equol (10 mg) on bone resorption. and transmitted securely. 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. Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells. 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. PV panels have been linked . However, the moonlight decreases after the full moon. 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. The two systematic reviews conclude that isoflavones have an important role in reducing hot flushes [52,53], although some observations need to be pointed out. Moreover, the number of publications grouping women according to pre- or post-diagnosis intake criteria is small. Lund S., Holman G.D., Schmitz O., Pedersen O. Sansai K., Na Takuathung M., Khatsri R., Teekachunhatean S., Hanprasertpong N., Koonrungsesomboon N. Effects of isoflavone interventions on bone mineral density in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. (2016), nine studies addressed to menopausal women and focused on bone health were analyzed [52]. 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. In addition, several studies have observed that the urine excretion of daidzein metabolites is notably higher than that of genistein metabolites [44,45,46]. Isoflavone excretion occurs mainly through urine and feces, primarily in the conjugate forms, and up to 95% takes place in 24 h [43]. Phenolic compounds are secondary metabolites, which are produced by plants as a defense mechanism against infection, water stress, cold stress, ultraviolet radiation and high visible light, among others [1,2]. Oral isoflavone supplementation on endometrial thickness: A meta-analysis of randomized placebo-controlled trials. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level. By contrast, the total isoflavone amount is high in soy flour, protein isolate or edamame [19]. Sansai et al. In contrast, the effects on bone resorption biomarkers were more favorable in overweight or obese women than in women with a healthy weight. However, the authors acknowledged several limitations to their study, such as the small sample size in the meta-analysis (middle-aged 276 women and 209 men), and recognized that a large number of subjects as well as a lengthier intervention are needed to investigate whether supplementation of soy isoflavones actually improves these outcomes. Atkinson C., Frankenfeld C.L., Lampe J.W. Sfakianos J., Coward L., Kirk M., Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. The main forms of conjugates in soybeans are the malonyl derivatives [14]. 19% reduction in endometrial cancer risk. (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]. Taken as a whole, all these results suggest that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. (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]. 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). However, more studies are required to provide stronger evidence. Moreover, an increase in thyroid hormone levels after isoflavone intake by food supplements has not been observed, and no side effects were confirmed with regard to the endometrial thickness or histopathological changes in the uterus. ); sue.uhe@zednanref.oderfla (A.F.-Q. Produced metabolites appear in plasma at variable concentrations and can enter enterohepatic circulation [28]. As it has been stated in the Bioavailability section, microbiota composition in humans makes equol production very variable, which yields high interindividual differences. In the end, isoflavones could be useful in reducing hot flushes associated with menopause. Lastly, Abshirini et al. 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). (2020) carried out their meta-analysis of 63 controlled trials, including 6427 postmenopausal women and concluded that isoflavones improve bone density at the lumbar spine, femoral neck and the distal radius in menopausal women [50]. (2016) also studied whether there was an association between different types of interventions and the reduction in hot flushes and night sweats [90]. 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. 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. The main isoflavones found in foodstuffs are daidzein, genistein and glycitein, as well as biochanin A and formononetin [9,12]. Another meta-analysis, conducted by Zhao et al. 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. 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. Kim Y., Je Y. Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. ; WritingReview and Editing, M.P.P., S.G.-Z., I.E. 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. Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract. Lambert M.N.T., Hu L.M., Jeppesen P.B. However, the authors stated that they could not reach definitive conclusions due to, among other reasons, the lack of inclusion in the review of randomized controlled clinical trials focused on the treatment of osteoporosis in early menopause. 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]. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Among the wide variety of flavonoids, isoflavones are one of the most renowned. In the meta-analysis reported by Chen et al. Isoflavones are found in several vegetables, mainly in legumes (Fabaceae family) such as soy, white and red clover, alfalfa and beans [9,10]. Conceptualization, S.G.-Z. 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. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. Bardin A., Boulle N., Lazennec G., Vignon F., Pujol P. Loss of ERbeta expression as a common step in estrogen-dependent tumor progression. You et al. Concerning this issue, six meta-analyses and two systematic reviews are included in the present review (Table 5). and J.T. Zhong et al. Abdi et al. Thanks for reading Scientific American. Due to the presence of biologically active compounds, walnut was used in the . Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in Korean women but not men: Results from the Korean Genome and Epidemiology Study. Kov L., Dadkov K., Kaparovsk J., Kaparovsk T. Isoflavones. Their meta-analysis included five studies with a total of 728 menopausal women between 50.5 and 58.5 years old and concluded that women who are not able to produce equol could benefit from equol supplementation. 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. Disease and all causes: a meta-analysis of randomized placebo-controlled trials Zheng Q ( 22 % vs. 18 %.. And rat liver and gastrointestinal tract effects of animal and plant-sourced proteins lipemia. Et al, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk with. 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