As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. 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. 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). According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. 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. (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]. Sfakianos J., Coward L., Kirk M., Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. 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. 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 . and A.F.-Q. van der Schouw Y.T., Kreijkamp-Kaspers S., Peeters P.H., Keinan-Boker L., Rimm E.B., Grobbee D.E. (2016) suggested that a daily intake of soy isoflavones, ranging from 20 to 100 mg/day, reduced total cholesterol and triglyceride plasma concentrations, as well as some markers of oxidative stress (nitric oxide and malonaldehyde), thus reducing cardiovascular risk [52]. Estimated Asian adult soy protein and isoflavone intakes. In Japanese men, pre-diagnostic circulating levels of genistein, daidzein and equol did not significantly affect prostate cancer risk. Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. Kov L., Dadkov K., Kaparovsk J., Kaparovsk T. Isoflavones. He X., Sun L.M. Bhathena S.J., Velasquez M.T. In view of the results gathered in the present review, we can conclude that there is scientific evidence that reveals the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis in postmenopausal women. Zhong et al. . Nevertheless, this association was not shown when equol or isoflavones were consumed. Others, however, consider such notions as prime examples of "New Age freakery". In this sense, the authors suggested that the composition of the gut microflora may influence isoflavone absorption and metabolism and could affect the production of isoflavone metabolites, which, in turn, could mediate their biological activity. Sarri G., Pedder H., Dias S., Guo Y., Lumsden M.A. Comparative efficacy of nonhormonal drugs on menopausal hot flashes. Soy products (0.05130 g/day) and total isoflavones (0.28 to 63 mg/day). 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. Acid rain leaches aluminum from the soil. and J.T. Future research in this field should quantify isoflavones as accurately as possible, analyzing larger cohorts and lengthening the follow-up stage. ); sue.uhe@zednanref.oderfla (A.F.-Q. As it has been stated in the Bioavailability section, microbiota composition in humans makes equol production very variable, which yields high interindividual differences. In this systematic review, 123 studies were included, with a total number of 516,330 participants. Effects of isoflavones in different cancer types. Looking at a few examples of moonlight's. The meta-analysis included 15 studies in which the number of participants ranged from 30 to 252. In this regard, it has been reported that isoflavones have a higher affinity to the -estrogen receptor [7], which, contrary to the -estrogen receptor, inhibits cell proliferation and stimulates apoptosis [84]. 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. With regard to the published meta-analysis, the studies included were restricted to randomized controlled trials. Dead or dying trees are a common sight in areas effected by acid rain. (2016) conducted a meta-analysis of 18 studies involving 16,917 colorectal cancer cases in 559,486 participants [78]. However, the intake of specific isoflavones, genistein and daidzein, was indeed significantly associated with a reduced risk of this type of cancer. 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). The enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. Yan Z., Zhang X., Li C., Jiao S., Dong W. Association between consumption of soy and risk of cardiovascular disease: A meta-analysis of observational studies. In addition, Qiu et al. Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. 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. Abdi et al. PV panels have been linked . 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. Daidzein is first converted into dihydrodaidzein, which is the precursor of both equol and O-demethylangolensin (O-DMA) [37]. Thanks for reading Scientific American. A total of 16 studies were included in their meta-analysis with a range of 24 to 236 subjects. Further, Chalvon-Demersay et al. Careers, Unable to load your collection due to an error. ), 2CIBEROBN Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, 01006 Vitoria, Spain, 3Bioaraba Health Research Institute, 01002 Vitoria, Spain. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Determination of total soy isoflavones in dietary supplements, supplement ingredients, and soy foods by high-performance liquid chromatography with ultraviolet detection: Collaborative study. Applegate C.C., Rowles J.L., Ranard K.M., Jeon S., Erdman J.W. Vasomotor symptoms resulting from natural menopause: A systematic review and network meta-analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause. In the last few decades, scientific evidence has stressed the importance of plants in the prevention and/or supportive treatment of a plethora of diseases, many of them chronic, age-associated disorders. Received 2020 Nov 30; Accepted 2020 Dec 15. (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 authors found a significant inverse association between isoflavone intake and both overall mortality and breast cancer recurrence. This is mainly due to their potential adverse effects, which range from increased coronary heart disease to stroke and cancer [53,85]. In fact, the number of isoflavones present was very variable among the different soy food types. Lund S., Holman G.D., Schmitz O., Pedersen O. In addition, genistein and glycitein are transformed into dihydrogenistein and dihydroglycitein, respectively, before being further converted into other metabolites. Simental-Menda L.E., Gotto A.M., Atkin S.L., Banach M., Pirro M., Sahebkar A. The authors reported that isoflavone intake from soy products and legumes was associated with a 19% reduction in endometrial cancer risk. However, when a subgroup analysis by a class of flavonoids was carried out, they concluded that these inverse associations were significant for all categories of flavonoids except for isoflavones and flavonols. 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]. Explore our digital archive back to 1845, including articles by more than 150 Nobel Prize winners. 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]. Equol has been considered as the most interesting colonic metabolite due to its beneficial biological activity, which differs from that of its precursor, daidzein [13,38,39]. However, a limitation in this field is that there is still a great heterogeneity among studies. In miso and tempeh, the aglycone form is the most abundant one [9]. 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. Continue reading with a Scientific American subscription. The light of the moon also influences animals that are active in daytime. In the aforementioned mechanism, it has been reported that isoflavones bind to both ER and ER, although they present a higher affinity towards ER receptors [7]. In fact, all the body fluids, as the tides, were controlled by the lunar phases. However, the authors suggested that more prospective cohort studies are needed to further investigate this association and that the quantity of isoflavone intake should be accurately measured because flavonoid contents in food can vary significantly. 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). [(accessed on 21 September 2020)]; Messina M., Nagata C., Wu A.H. (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]. 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. Wang X., Dykens J.A., Perez E., Liu R., Yang S., Covey D.F., Simpkins J.W. Inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, but not in cohort studies. (2016), nine studies addressed to menopausal women and focused on bone health were analyzed [52]. Background Climate change and the current phase-out of fossil fuel-fired power generation are currently expanding the market of renewable energy and more especially photovoltaic (PV) panels. 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. Perna S., Peroni G., Miccono A., Riva A., Morazzoni P., Allegrini P., Preda S., Baldiraghi V., Guido D., Rondanelli M. Multidimensional Effects of Soy Isoflavone by Food or Supplements in Menopause Women: A Systematic Review and Bibliometric Analysis. 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. Hua et al. The most significant food source of isoflavones in humans is soy-derived products. This result has implications for granivory and perhaps plant demography in invaded and restored coastal habitats. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The main isoflavones found in foodstuffs are daidzein, genistein and glycitein, as well as biochanin A and formononetin [9,12]. Adlercreutz H., Markkanen H., Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Treutter D. Significance of flavonoids in plant resistance and enhancement of their biosynthesis. Furthermore, isoflavones are able to inhibit aromatase activity, the enzyme that converts androgen to estrogen. Overall, evidence regarding the use of isoflavones in cancer prevention suggests that they may be useful in reducing the risk of suffering from some types of cancer, such as breast and endometrial cancer, two of the types for which the association between isoflavone intake and cancer risk has been studied more in-depth. van Erp-Baart M.A., Brants H.A., Kiely M., Mulligan A., Turrini A., Sermoneta C., Kilkkinen A., Valsta L.M. They also note that the effects of isoflavones are greater when administered as aglycones. Thirty-nine studies were included with a sample size of 200 women per trial, in which the intervention period ranged from two to 96 weeks (median 12 weeks). Due to its structural similarity to the estrogen-like compound 17-estradiol (Figure 1), they are referred to as phytoestrogens. 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. Implications of phytoestrogen intake for breast cancer. Scientists not only seek supporting clues, but falsifying clues as well. Duffy C., Perez K., Partridge A. Lu D., Gigure V. Requirement of Ras-dependent pathways for activation of the transforming growth factor beta3 promoter by estradiol. For this reason, the bioavailability of isoflavones has been extensively characterized in animal models and humans [25,26,27]. Isoflavones were the phytoestrogens used in most of the studies; therefore, the meta-analysis only included outcomes regarding isoflavones, while outcomes with other phytoestrogens were not included. Create your free account or Sign in to continue. Santo A.S., Santo A.M., Browne R.W., Burton H., Leddy J.J., Horvath S.M., Horvath P.J. (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]. Postprandial lipemia detects the effect of soy protein on cardiovascular disease risk compared with the fasting lipid profile. Lastly, Zhang et al. The authors suggested that this difference could be due to different genetic backgrounds and dietary patterns among Asian and Western populations. Rizzo G., Baroni L. Soy, Soy Foods and Their Role in Vegetarian Diets. 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. In this line, three meta-analyses were conducted to study isoflavone consumption and endometrial cancer risk. Although smaller in quantity, isoflavones are also present in chickpeas, nuts, fruits and vegetables [11]. 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. (2017) included 26 trials with 2652 participants [48]. Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. But that doesn't mean that they dig in their heels and argue about it. Due to the presence of biologically active compounds, walnut was used in the . Furthermore, isoflavones are associated with proteins; thus, alcohol extraction and processing diminish isoflavone content in foodstuffs such as fermented soybean, tofu or soy beverages. 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]. They observed that daidzein and genistein intakes were associated with a significant reduction of prostate cancer risk. A significant 19% reduction of the risk was found at high concentrations of daidzein, but not at genistein or equol concentrations. The physical stiffening of arteries has major health implications for its connection to various adverse cardiovascular and other health outcomes such as coronary heart disease, stroke, hypertension or heart failure [66]. Li L., Lv Y., Xu L., Zheng Q. Quantitative efficacy of soy isoflavones on menopausal hot flashes. With regard to prostate cancer, it has been proposed that it might be affected by isoflavone consumption due to its effect on hormone metabolism. Thus, its consumption, according to epidemiological and clinical studies, has been postulated to be related to a decrease in the risk of different diseases. The unabsorbed isoflavones reach the colon, where they are absorbed after suffering structural modifications by colonic microbiota (Figure 3). In any case, it is important to bear in mind that a great number of expert scientists and doctors think that breast cancer survivors should not increase their isoflavone intake [94], although others consider that their consumption is safe and beneficial [95]. 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. Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract. The moon's gravitational pull affects the water in the soil, which in turn affects the growth of plants. 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. 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]. 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). 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