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]. 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. In this line, three meta-analyses were conducted to study isoflavone consumption and endometrial cancer risk. In some Asian countries, isoflavone intake, usually derived from soy consumption, can be associated with a lower prevalence of cardiovascular diseases (CVDs). Zaheer K., Humayoun Akhtar M. An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health. The authors reported that neither soy food intake nor circulating isoflavones were associated with a reduced risk of prostate cancer. In contrast, it seems that isoflavones do not act on central neurotransmitters directly. 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. 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]. Concerning this issue, six meta-analyses and two systematic reviews are included in the present review (Table 5). That aluminum may be harmful to plants as well as animals. Daily et al. 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). Perna et al. In the meta-analysis reported by Chen et al. Isoflavone glycosides have to be hydrolyzed to the aglycone form prior to its absorption by passive diffusion in the upper small intestine [28]. The aim of the present review is to gather the scientific evidence existing nowadays on the main beneficial effects of isoflavones on health: bone health, cardiovascular risk, cancer and menopausal symptoms. Effects of isoflavones in cardiovascular disease-related markers. 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. HHS Vulnerability Disclosure, Help Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. With regard to the published meta-analysis, the studies included were restricted to randomized controlled trials. Daidzein is first converted into dihydrodaidzein, which is the precursor of both equol and O-demethylangolensin (O-DMA) [37]. Taken as a whole, all these results suggest that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. 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. [(accessed on 21 September 2020)]; Messina M., Nagata C., Wu A.H. Effects of isoflavones in different cancer types. Qiu S., Jiang C. Soy and isoflavones consumption and breast cancer survival and recurrence: A systematic review and meta-analysis. Reproductive and developmental toxicity studies have stated that 1 g and 2 g of equol per day is safe [96], although further studies are required [92]. Equol is produced from the isoflavone daidzein by intestinal bacteria, mainly in the large intestine. 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. Vlachopoulos C., Aznaouridis K., Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: A systematic review and meta-analysis. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. Nevertheless, it is important to consider this metabolite since it is key in the biological activity of isoflavones [13]. and J.T. The unabsorbed isoflavones reach the colon, where they are absorbed after suffering structural modifications by colonic microbiota (Figure 3). At high elevations, acidic fog and clouds might . For the development of this section, the meta-analyses and systematic reviews published between 2015 and 2020 were taken into account. The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. Gruber C.J., Tschugguel W., Schneeberger C., Huber J.C. Production and actions of estrogens. Collison M.W. Phytoestrogen Metabolism by Adult Human Gut Microbiota. Estimated Asian adult soy protein and isoflavone intakes. 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. 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]. 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. Furthermore, soy protein has been linked to an improvement in nitric oxide production and contributes to increased arterial compliance [65]. THE effect of light on plant life has been the subject of many scientific investigations. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: A meta-analysis of prospective studies. Moonlight sonata. 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. Potential health adverse effects in the intake of isoflavones have been postulated due to their estrogenic activity, especially in relation to breast cancer. 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. 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. 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. 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. 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. Altogether, these results show that further studies are needed in order to find stronger conclusions. They observed that it was dose-dependent at low to moderate soybean consumption. With regard to prostate cancer, it has been proposed that it might be affected by isoflavone consumption due to its effect on hormone metabolism. Grosso et al. The authors indicated that high concentrations of daidzein and genistein (no specific values concerning these concentrations were available) were related to 34% and 28% reduction in breast cancer risk, respectively, whereas no association with equol was found. 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. Lastly, Abshirini et al. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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. The authors declare no conflict of interest. For this reason, the bioavailability of isoflavones has been extensively characterized in animal models and humans [25,26,27]. Chadha R., Bhalla Y., Jain A., Chadha K., Karan M. Dietary Soy Isoflavone: A Mechanistic Insight. 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. Although smaller in quantity, isoflavones are also present in chickpeas, nuts, fruits and vegetables [11]. 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. 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. A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women. Professor Piazza Smyth, the Astronomer Royal for Scotland, in his interesting account of a recent scientific expedition made by him to the Peak of Teneriffe, has set at rest the vexed question of the heat of the moonlight. 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 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]. Explore our digital archive back to 1845, including articles by more than 150 Nobel Prize winners. The results indicated that the isoflavone intake decreased the ovarian cancer risk by 33%. Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. Simental-Menda L.E., Gotto A.M., Atkin S.L., Banach M., Pirro M., Sahebkar A. 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. 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. Moreover, even though the binding affinity of isoflavones to the ER receptors is less than that of 17-estradiol, they can also act as estrogenic compounds when the endogenous estradiol is not available [8]. In the same line, Yu et al. Thus, its consumption, according to epidemiological and clinical studies, has been postulated to be related to a decrease in the risk of different diseases. (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]. Association of isoflavone biomarkers with risk of chronic disease and mortality: A systematic review and meta-analysis of observational studies. 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. (2019) studied whether equol supplementation could benefit equol nonproducer subjects in lowering the incidence and severity of hot flushes [85]. Soy Consumption and the Risk of Prostate Cancer: An Updated Systematic Review and Meta-Analysis. 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. (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]. However, the intake of specific isoflavones, genistein and daidzein, was indeed significantly associated with a reduced risk of this type of cancer. Received 2020 Nov 30; Accepted 2020 Dec 15. Soy isoflavones and their metabolites modulate cytokine-induced natural killer cell function. The main isoflavones found in foodstuffs are daidzein, genistein and glycitein, as well as biochanin A and formononetin [9,12]. aimed to compare the effects of animal and plant-sourced proteins on lipemia and blood pressure [60]. The work reported by Lambert et al. Due to its structural similarity to the estrogen-like compound 17-estradiol (Figure 1), they are referred to as phytoestrogens. 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. As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. However, the moonlight decreases after the full moon. 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). The https:// ensures that you are connecting to the In like manner, a meta-analysis by Simental-Menda et al. 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 the meta-analysis reported by Applegate et al. (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]. 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 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. ); [email protected] (A.F.-Q. Cheynier V., Sarni-Manchado P., Quideau S., editors. Lambert M.N.T., Hu L.M., Jeppesen P.B. 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. 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. After this, each metabolite undergoes its own metabolic pathway [40]. (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]. Knowledge awaits. Hua X., Yu L., You R., Yang Y., Liao J., Chen D. Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis. (2016) included 17 studies (nine case-control studies and eight cohort studies) [80]. Metabolites of dietary (soya) isoflavones in human urine. (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 general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. 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]. However, it is important to mention that this connection has been established based on pre-clinical studies, whereas data derived from clinical trials have not demonstrated such association [92]. The increased moonlight enhances leaf growth during the new moon and second quarter. Metabolism of intraruminally administered [4-. The dose of isoflavones ranged from 30 to 200 mg/day. Efficacy of phytoestrogens for menopausal symptoms: A meta-analysis and systematic review. (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]. Due to the high prevalence of colorectal cancer, three meta-analyses addressing this issue are included in the present review. For this reason, the results should be interpreted with caution, and more randomized clinical trials are imperative. Gee J.M., DuPont M.S., Day A.J., Plumb G.W., Williamson G., Johnson I.T. . However, all the authors agree that further studies are necessary so as to confirm these results. Moreover, the authors suggested that ethnicity could have had influenced this association, but studies with larger sample sizes are needed to confirm this hypothesis. Due to the presence of biologically active compounds, walnut was used in the . In this section, 16 meta-analyses have been revised: Nachvack et al. By contrast, the total isoflavone amount is high in soy flour, protein isolate or edamame [19]. Further, Chalvon-Demersay et al. But that doesn't mean that they dig in their heels and argue about it. 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. (2019), included 16 prospective cohort studies involving 11,169 breast cancer cases and 648,913 participants [70]. 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. 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. 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. As previously mentioned, soybeans and their derived foodstuffs are the main isoflavone sources in the human diet, at least if we do not consider red clover extract supplements, which are being widely used by menopausal women as nutraceutical therapy [13]. 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; [email protected] (S.G.-Z. 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]. Potential mechanism of action of isoflavones on bone metabolism. (2018), 30 articles were included for analysis; 15 of them were case-control studies, eight cohort studies and seven nested case-control studies [76]. Furthermore, isoflavones are associated with proteins; thus, alcohol extraction and processing diminish isoflavone content in foodstuffs such as fermented soybean, tofu or soy beverages. Create your free account or Sign in to continue. Hairi H.A., Shuid A.N., Ibrahim N., Jamal J.A., Mohamed N., Mohamed I.N. Thanks for reading Scientific American. Dietary intake of flavonoid subclasses and risk of colorectal cancer: Evidence from population studies. Estradiol, which has proven efficacy on hot flushes, needs 3.09 weeks to achieve half of its peak activity, while isoflavones require 13.4 weeks, suggesting that 12 weeks of treatment is not enough for soy isoflavones to exert a beneficial effect. Although results vary greatly, most of these applications are supported by at least a few clinical studies. This fact suggests that other components, such as fiber in the soy foods, may account for these negative associations. 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