In the same line, in European men, isoflavone concentrations did not affect the risk of developing prostate cancer. Moreover, five studies reported side-effect data, and after the analysis, no significant differences were observed between the two groups. However, the intake of specific isoflavones, genistein and daidzein, was indeed significantly associated with a reduced risk of this type of cancer. 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. The dose of isoflavones ranged from 30 to 200 mg/day. THE effect of light on plant life has been the subject of many scientific investigations. With regard to the published meta-analysis, the studies included were restricted to randomized controlled trials. 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. In: Thompson M.J., editor. 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. Bacterial metabolites of isoflavones forming in the gut. Potential mechanism of action of isoflavones on bone metabolism. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. 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). 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. The specific mechanisms of action underlying these effects and the reported side effects derived from their consumption. Daidzein is first converted into dihydrodaidzein, which is the precursor of both equol and O-demethylangolensin (O-DMA) [37]. The main forms of conjugates in soybeans are the malonyl derivatives [14]. Liu J., Yuan F., Gao J., Shan B., Ren Y., Wang H., Gao Y. 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. U.S. Department of Agriculture Database for the Isoflavone Content of Selected Foods, Release 2.0. Isoflavones are found in several vegetables, mainly in legumes (Fabaceae family) such as soy, white and red clover, alfalfa and beans [9,10]. Yu Y., Jing X., Li H., Zhao X., Wang D. Soy isoflavone consumption and colorectal cancer risk: A systematic review and meta-analysis. However, more studies are required to provide stronger evidence. 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. However, a limitation in this field is that there is still a great heterogeneity among studies. The .gov means its official. Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. Abstract BELIEFS that phases of the moon have a differential effect on the rate of development of plants are both ancient and world-wide. In addition, genistein and glycitein are transformed into dihydrogenistein and dihydroglycitein, respectively, before being further converted into other metabolites. Thus, soybean can be considered as the best food source. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. Consequently, isoflavones can have estrogenic or anti-estrogenic effects [3]. They also note that the effects of isoflavones are greater when administered as aglycones. HHS Vulnerability Disclosure, Help ; WritingReview and Editing, M.P.P., S.G.-Z., I.E. In this study, five prospective cohort studies and seven case-control studies, with 6275 cases and 393,776 controls, were included. Arjmandi B.H., Smith B.J. Further, Chalvon-Demersay et al. 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. Isoflavones have received attention due to their putative healthy properties. 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. 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. (2020) revealed that supplementation of soy isoflavones had a positive effect in reducing arterial stiffness, also known as the loss of arterial elasticity [59]. Thus, its consumption, according to epidemiological and clinical studies, has been postulated to be related to a decrease in the risk of different diseases. 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. (2017) included 26 trials with 2652 participants [48]. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Rizzo G., Baroni L. Soy, Soy Foods and Their Role in Vegetarian Diets. Produced metabolites appear in plasma at variable concentrations and can enter enterohepatic circulation [28]. 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). Before (2016) conducted a meta-analysis aimed at ovarian cancer, which affects women exclusively [74]. Altogether, these results show that further studies are needed in order to find stronger conclusions. (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]. At high elevations, acidic fog and clouds might . In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. Non-pharmacological treatments included isoflavones, which appeared to be better than placebo in the relief of vasomotor symptoms, although not significantly better than the treatment with estradiol and progesterone. (2017) carried out a meta-analysis of 143 case-control studies, where isoflavone intake was associated with endometrial, ovarian, and breast cancers [73]. (2019) studied whether equol supplementation could benefit equol nonproducer subjects in lowering the incidence and severity of hot flushes [85]. While a moderate intake of soy isoflavones did not significantly affect breast cancer risk, a significant reduction was shown when the intake was high. (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]. Sirotkin A.V., Harrath A.H. Phytoestrogens and their effects. (2016), nine studies addressed to menopausal women and focused on bone health were analyzed [52]. Thus, the EFSA scientific committees opinion agreed that isoflavone intake was safe, at least in the doses that the analyzed studies have used. EFSA Pannel on Food Additives and Nutrient Sources Added to Food (ANS) Risk assessment for peri- and post-menopausal women taking food su pplements containing isola ted isoflavones. This difference could explain the slow effect of isoflavones in alleviating hot flushes. Zhong et al. As it has been stated in the Bioavailability section, microbiota composition in humans makes equol production very variable, which yields high interindividual differences. Hence, plants grow faster and healthier. The association between dietary isoflavones intake and gastric cancer risk: A meta-analysis of epidemiological studies. 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). Four meta-analyses have been reported to address this issue. 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. 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. Phytoestrogen Metabolism by Adult Human Gut Microbiota. Looking at a few examples of moonlight's. The improvement was greater in treatments lasting more than one year and in subjects with normal weight, probably because subjects with excessive body weight have a lesser risk of bone loss. As with other phenolic compounds, isoflavones can be presented as free forms (aglycones) or conjugated with carbohydrates (glycosides). (2016) conducted a meta-analysis of 18 studies involving 16,917 colorectal cancer cases in 559,486 participants [78]. 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